DOI: 10.7554/elife.01489. Structural basis for the prion-like MAVS filaments in antiviral innate immunity

Structural basis for the prion-like MAVS filaments in antiviral innate immunity

10.7554/elife.01489

Crossref journal-article

eLife Sciences Publications, Ltd

eLife (4374)

Abstract

Mitochondrial antiviral signaling (MAVS) protein is required for innate immune responses against RNA viruses. In virus-infected cells MAVS forms prion-like aggregates to activate antiviral signaling cascades, but the underlying structural mechanism is unknown. Here we report cryo-electron microscopic structures of the helical filaments formed by both the N-terminal caspase activation and recruitment domain (CARD) of MAVS and a truncated MAVS lacking part of the proline-rich region and the C-terminal transmembrane domain. Both structures are left-handed three-stranded helical filaments, revealing specific interfaces between individual CARD subunits that are dictated by electrostatic interactions between neighboring strands and hydrophobic interactions within each strand. Point mutations at multiple locations of these two interfaces impaired filament formation and antiviral signaling. Super-resolution imaging of virus-infected cells revealed rod-shaped MAVS clusters on mitochondria. These results elucidate the structural mechanism of MAVS polymerization, and explain how an α-helical domain uses distinct chemical interactions to form self-perpetuating filaments.

Bibliography

Xu, H., He, X., Zheng, H., Huang, L. J., Hou, F., Yu, Z., de la Cruz, M. J., Borkowski, B., Zhang, X., Chen, Z. J., & Jiang, Q.-X. (2014). Structural basis for the prion-like MAVS filaments in antiviral innate immunity. ELife, 3. CLOCKSS.

Authors 11

Hui Xu (first)
Xiaojing He (additional)
Hui Zheng (additional)
Lily J Huang (additional)
Fajian Hou (additional)
Zhiheng Yu (additional)
Michael Jason de la Cruz (additional)
Brian Borkowski (additional)
Xuewu Zhang (additional)
Zhijian J Chen (additional)
Qiu-Xing Jiang (additional)

References 67 Referenced 152

10.1107/S0907444902016657 / Acta Crystallographica Section D Biological Crystallography / PHENIX: building new software for automated crystallographic structure determination by Adams (2002)
10.1038/emboj.2012.19 / The EMBO Journal / MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA by Berke (2012)
10.1038/embor.2009.258 / EMBO Reports / Mitochondrial dynamics regulate the RIG-I-like receptor antiviral pathway by Castanier (2010)
10.1038/embor.2011.190 / EMBO Reports / The RIG-I ATPase domain structure reveals insights into ATP-dependent antiviral signalling by Civril (2011)
10.1016/j.jsb.2006.05.015 / Journal of Structural Biology / The iterative helical real space reconstruction method: surmounting the problems posed by real polymers by Egelman (2007)
10.1107/S0907444904019158 / Acta Crystallographica Section D Biological Crystallography / Coot: model-building tools for molecular graphics by Emsley (2004)
10.1107/S0907444910007493 / Acta Crystallographica Section D Biological Crystallography / Features and development of Coot by Emsley (2010)
10.1016/j.sbi.2010.03.011 / Current Opinion in Structural Biology / SF1 and SF2 helicases: family matters by Fairman-Williams (2010)
10.1093/acprof:oso/9780195182187.001.0001 / Three-dimensional electron microscopy of macromolecular assemblies by Frank (2006)
10.1016/j.immuni.2009.06.014 / Immunity / A nonself RNA pattern: tri-p to panhandle by Fujita (2009)
10.1016/j.it.2010.12.005 / Trends in immunology / What the Myddosome structure tells us about the initiation of innate immunity by Gay (2011)
10.1529/biophysj.107.120345 / Biophysical Journal / Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination by Gustafsson (2008)
10.1016/j.str.2007.12.017 / Structure / Regulation of enzyme localization by polymerization: polymer formation by the SAM domain of diacylglycerol kinase delta1 by Harada (2008)
10.1073/pnas.0906923106 / Proceedings of the National Academy of Sciences of the United States of America / Crystal structure of the plexin A3 intracellular region reveals an autoinhibited conformation through active site sequestration by He (2009)
10.1039/c0nr00615g / Nanoscale / Two-layer membranes of calcium phosphate/collagen/PLGA nanofibres: in vitro biomineralisation and osteogenic differentiation of human mesenchymal stem cells by Hild (2011)
10.1126/science.1132505 / Science / 5’-Triphosphate RNA is the ligand for RIG-I by Hornung (2006)
10.1016/j.cell.2011.06.041 / Cell / MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response by Hou (2011)
10.1126/science.1183021 / Science / Regulation of adaptive immunity by the innate immune system by Iwasaki (2010)
10.1007/978-1-61779-166-6_9 / Methods in Molecular Biology / Electron microscopic imaging of integrin by Iwasaki (2012)
10.1038/nature10537 / Nature / Structural basis of RNA recognition and activation by innate immune receptor RIG-I by Jiang (2011)
10.1016/j.immuni.2012.03.022 / Immunity / Ubiquitin-induced oligomerization of the RNA sensors RIG-I and MDA5 activates antiviral innate immune response by Jiang (2012)
10.1084/jem.20080091 / The Journal of Experimental Medicine / Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5 by Kato (2008)
{'key': 'bib23', 'first-page': '1231', 'article-title': '[Role of IPS-1 in type I IFN induction]', 'volume': '64', 'author': 'Kawai', 'year': '2006', 'journal-title': 'Nihon Rinsho Japanese Journal of Clinical Medicine'} / Nihon Rinsho Japanese Journal of Clinical Medicine / [Role of IPS-1 in type I IFN induction] by Kawai (2006)
10.1038/ni1243 / Nature Immunology / IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction by Kawai (2005)
10.1016/j.tibs.2011.06.006 / Trends in Biochemical Sciences / The death-fold superfamily of homotypic interaction motifs by Kersse (2011)
10.1038/embor.2013.108 / EMBO Reports / Defining the functional determinants for RNA surveillance by RIG-I by Kohlway (2013)
10.1126/scisignal.2001147 / Science signaling / Mitochondrial membrane potential is required for MAVS-mediated antiviral signaling by Koshiba (2011)
10.1016/j.cell.2011.09.039 / Cell / Structural basis for the activation of innate immune pattern-recognition receptor RIG-i by viral RNA by Kowalinski (2011)
10.1099/vir.0.032367-0 / The Journal of General Virology / RNA helicase retinoic acid-inducible gene I as a sensor of Hantaan virus replication by Lee (2011)
10.1038/nature09121 / Nature / Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling by Lin (2010)
10.7554/eLife.00785 / eLife / MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades by Liu (2013)
10.1128/JVI.01080-07 / Journal of Virology / Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity by Loo (2008)
10.1006/jsbi.1999.4174 / Journal of Structural Biology / EMAN: semiautomated software for high-resolution single-particle reconstructions by Ludtke (1999)
10.1016/j.cell.2011.09.023 / Cell / Structural insights into RNA recognition by RIG-I by Luo (2011)
10.4161/rna.22706 / RNA Biology / Duplex RNA activated ATPases (DRAs): platforms for RNA sensing, signaling and processing by Luo (2013)
10.1016/j.str.2012.08.029 / Structure / Visualizing the determinants of viral RNA recognition by innate immune sensor RIG-I by Luo (2012)
10.1074/jbc.M110.186262 / The Journal of Biological Chemistry / Short double-stranded RNAs with an overhanging 5’ ppp-nucleotide, as found in arenavirus genomes, act as RIG-I decoys by Marq (2011)
10.1107/S0021889807021206 / Journal of Applied Crystallography / Phaser crystallographic software by McCoy (2007)
10.1038/nature04193 / Nature / Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus by Meylan (2005)
10.1073/pnas.97.22.11910 / Proceedings of the National Academy of Sciences of the United States of America / A census of glutamine/asparagine-rich regions: implications for their conserved function and the prediction of novel prions by Michelitsch (2000)
10.1038/nature12729 / Nature / Antibacterial membrane attack by a pore-forming intestinal C-type lectin by Mukherjee (2014)
10.1074/jbc.M800542200 / The Journal of Biological Chemistry / Structure and function of LGP2, a DEX(D/H) helicase that regulates the innate immunity response by Murali (2008)
10.1146/annurev-biophys-083012-130338 / Annual Review of Biophysics / Molecular basis of NF-kappaB signaling by Napetschnig (2013)
10.1038/nature03680 / Nature / Structure of the cross-beta spine of amyloid-like fibrils by Nelson (2005)
10.1073/pnas.97.19.10395 / Proceedings of the National Academy of Sciences of the United States of America / Molecular basis for CD40 signaling mediated by TRAF3 by Ni (2000)
10.1371/journal.ppat.1001012 / PLoS Pathogens / Virus-infection or 5’ppp-RNA activates antiviral signal through redistribution of IPS-1 mediated by MFN1 by Onoguchi (2010)
10.1016/S0076-6879(97)76066-X / Methods in Enzymology / Processing of X-ray diffraction data collected in oscillation mode by Otwinowski (1997)
10.1038/19110 / Nature / Structural basis for self-association and receptor recognition of human TRAF2 by Park (1999)
10.1038/embor.2013.102 / EMBO Reports / ATPase-driven oligomerization of RIG-I on RNA allows optimal activation of type-I interferon by Patel (2013)
10.1073/pnas.1113651108 / Proceedings of the National Academy of Sciences of the United States of America / Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition by Peisley (2011)
10.1016/j.molcel.2013.07.024 / Molecular Cell / RIG-I forms signaling-competent filaments in an ATP-dependent, ubiquitin-independent manner by Peisley (2013)
10.1002/jcc.20084 / Journal of Computational Chemistry / UCSF Chimera–a visualization system for exploratory research and analysis by Pettersen (2004)
10.1186/1472-6807-8-11 / BMC Structural Biology / Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain by Potter (2008)
10.1074/jbc.M806219200 / The Journal of Biological Chemistry / Agonist and antagonist recognition by RIG-I, a cytoplasmic innate immunity receptor by Ranjith-Kumar (2009)
10.1126/science.1189468 / Science / Plant and animal sensors of conserved microbial signatures by Ronald (2010)
10.1016/j.immuni.2009.05.008 / Immunity / Recognition of 5’ triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus by Schlee (2009)
10.1016/j.cell.2005.08.012 / Cell / Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3 by Seth (2005)
10.1016/j.cell.2010.01.022 / Cell / Pattern recognition receptors and inflammation by Takeuchi (2010)
10.1007/s12551-009-0026-3 / Biophysical Reviews / Using Situs for the integration of multi-resolution structures by Wriggers (2010)
10.1016/j.cell.2012.11.048 / Cell / Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5 by Wu (2013)
10.1016/j.molcel.2005.08.014 / Molecular Cell / VISA is an adapter protein required for virus-triggered IFN-beta signaling by Xu (2005)
10.1126/scisignal.2000287 / Science signaling / Mitofusin 2 inhibits mitochondrial antiviral signaling by Yasukawa (2009)
10.1111/j.1600-065X.2008.00727.x / Immunological Review / RNA recognition and signal transduction by RIG-I-like receptors by Yoneyama (2009)
10.1038/ni1087 / Nature Immunology / The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses by Yoneyama (2004)
10.1016/j.jmb.2012.10.006 / Journal of Molecular Biology / Unclosed HIV-1 capsids suggest a curled sheet model of assembly by Yu (2013)
10.1016/j.cell.2010.03.029 / Cell / Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity by Zeng (2010)
10.1016/j.molcel.2010.03.009 / Molecular Cell / Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: affinity, specificity, and regulation by Zheng (2010)

Dates

Type	When
Created	11 years, 6 months ago (Feb. 25, 2014, 11:23 a.m.)
Deposited	1 year, 10 months ago (Oct. 11, 2023, 8:43 p.m.)
Indexed	4 weeks, 1 day ago (July 30, 2025, 1:07 p.m.)
Issued	11 years, 6 months ago (Feb. 25, 2014)
Published	11 years, 6 months ago (Feb. 25, 2014)
Published Online	11 years, 6 months ago (Feb. 25, 2014)

Funders 20

National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. R01 GM088745
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. R01GM093271
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. R01GM088197
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. 1S10RR027972
American Heart Association 10.13039/100000968
Region: Americas
gov (Associations and societies (private and public))
Labels5
1. American Heart Association, Inc.
2. AMERICAN HEART ASSOC.
3. American Heart Assn
4. Association for the Prevention and Relief of Heart Disease
5. AHA
Awards1
1. 12IRG9400019
Welch
Awards1
1. I-1684, I-1389, and I-1702
Cancer Prevention Research Institute of Texas 10.13039/100004917 Cancer Prevention and Research Institute of Texas
Region: Americas
gov (National government)
Labels5
1. Cancer Prevention Research Institute of Texas
2. Cancer Prevention & Research Institute of Texas
3. The Cancer Prevention and Research Institute of Texas
4. CPRITTexas
5. CPRIT
Awards1
1. RP120474
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. R01 AI093967
Howard Hughes Medical Institute 10.13039/100000011
Region: Americas
pri (Research institutes and centers)
Labels2
1. Howard Hughes Medical Institute Inc
2. HHMI
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. C06RR30414
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. R01 GM088745
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. R01GM093271
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. R01GM088197
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. 1S10RR027972
American Heart Association 10.13039/100000968
Region: Americas
gov (Associations and societies (private and public))
Labels5
1. American Heart Association, Inc.
2. AMERICAN HEART ASSOC.
3. American Heart Assn
4. Association for the Prevention and Relief of Heart Disease
5. AHA
Awards1
1. 12IRG9400019
Welch Foundation 10.13039/100000928
Region: Americas
pri (Trusts, charities, foundations (both public and private))
Labels3
1. The Welch Foundation
2. Robert A. Welch Foundation
3. The Robert A. Welch Foundation
Awards1
1. I-1684, I-1389, and I-1702
Cancer Prevention and Research Institute of Texas 10.13039/100004917
Region: Americas
gov (National government)
Labels5
1. Cancer Prevention Research Institute of Texas
2. Cancer Prevention & Research Institute of Texas
3. The Cancer Prevention and Research Institute of Texas
4. CPRITTexas
5. CPRIT
Awards1
1. RP120474
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. R01 AI093967
Howard Hughes Medical Institute 10.13039/100000011
Region: Americas
pri (Research institutes and centers)
Labels2
1. Howard Hughes Medical Institute Inc
2. HHMI
National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
Labels3
1. Institutos Nacionales de la Salud
2. US National Institutes of Health
3. NIH
Awards1
1. C06RR30414

BibTeX

@article{Xu_2014, title={Structural basis for the prion-like MAVS filaments in antiviral innate immunity}, volume={3}, ISSN={2050-084X}, url={http://dx.doi.org/10.7554/elife.01489}, DOI={10.7554/elife.01489}, journal={eLife}, publisher={eLife Sciences Publications, Ltd}, author={Xu, Hui and He, Xiaojing and Zheng, Hui and Huang, Lily J and Hou, Fajian and Yu, Zhiheng and de la Cruz, Michael Jason and Borkowski, Brian and Zhang, Xuewu and Chen, Zhijian J and Jiang, Qiu-Xing}, year={2014}, month=feb }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        30
      ]
    ],
    "date-time": "2025-07-30T17:07:41Z",
    "timestamp": 1753895261439,
    "version": "3.41.2"
  },
  "reference-count": 67,
  "publisher": "eLife Sciences Publications, Ltd",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2014,
            2,
            25
          ]
        ],
        "date-time": "2014-02-25T00:00:00Z",
        "timestamp": 1393286400000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://creativecommons.org/licenses/by/3.0/"
    },
    {
      "start": {
        "date-parts": [
          [
            2014,
            2,
            25
          ]
        ],
        "date-time": "2014-02-25T00:00:00Z",
        "timestamp": 1393286400000
      },
      "content-version": "am",
      "delay-in-days": 0,
      "URL": "http://creativecommons.org/licenses/by/3.0/"
    },
    {
      "start": {
        "date-parts": [
          [
            2014,
            2,
            25
          ]
        ],
        "date-time": "2014-02-25T00:00:00Z",
        "timestamp": 1393286400000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "http://creativecommons.org/licenses/by/3.0/"
    },
    {
      "start": {
        "date-parts": [
          [
            2014,
            2,
            25
          ]
        ],
        "date-time": "2014-02-25T00:00:00Z",
        "timestamp": 1393286400000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://creativecommons.org/licenses/by/3.0/"
    },
    {
      "start": {
        "date-parts": [
          [
            2014,
            2,
            25
          ]
        ],
        "date-time": "2014-02-25T00:00:00Z",
        "timestamp": 1393286400000
      },
      "content-version": "am",
      "delay-in-days": 0,
      "URL": "http://creativecommons.org/licenses/by/3.0/"
    },
    {
      "start": {
        "date-parts": [
          [
            2014,
            2,
            25
          ]
        ],
        "date-time": "2014-02-25T00:00:00Z",
        "timestamp": 1393286400000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "http://creativecommons.org/licenses/by/3.0/"
    }
  ],
  "funder": [
    {
      "DOI": "10.13039/100000002",
      "name": "National Institutes of Health",
      "doi-asserted-by": "crossref",
      "award": [
        "R01 GM088745"
      ],
      "id": [
        {
          "id": "10.13039/100000002",
          "id-type": "DOI",
          "asserted-by": "crossref"
        }
      ]
    },
    {
      "DOI": "10.13039/100000002",
      "name": "National Institutes of Health",
      "doi-asserted-by": "crossref",
      "award": [
        "R01GM093271"
      ],
      "id": [
        {
          "id": "10.13039/100000002",
          "id-type": "DOI",
          "asserted-by": "crossref"
        }
      ]
    },
    {
      "DOI": "10.13039/100000002",
      "name": "National Institutes of Health",
      "doi-asserted-by": "crossref",
      "award": [
        "R01GM088197"
      ],
      "id": [
        {
          "id": "10.13039/100000002",
          "id-type": "DOI",
          "asserted-by": "crossref"
        }
      ]
    },
    {
      "DOI": "10.13039/100000002",
      "name": "National Institutes of Health",
      "doi-asserted-by": "crossref",
      "award": [
        "1S10RR027972"
      ],
      "id": [
        {
          "id": "10.13039/100000002",
          "id-type": "DOI",
          "asserted-by": "crossref"
        }
      ]
    },
    {
      "DOI": "10.13039/100000968",
      "name": "American Heart Association",
      "doi-asserted-by": "crossref",
      "award": [
        "12IRG9400019"
      ],
      "id": [
        {
          "id": "10.13039/100000968",
          "id-type": "DOI",
          "asserted-by": "crossref"
        }
      ]
    },
    {
      "name": "Welch",
      "award": [
        "I-1684, I-1389, and I-1702"
      ]
    },
    {
      "DOI": "10.13039/100004917",
      "name": "Cancer Prevention Research Institute of Texas",
      "doi-asserted-by": "crossref",
      "award": [
        "RP120474"
      ],
      "id": [
        {
          "id": "10.13039/100004917",
          "id-type": "DOI",
          "asserted-by": "crossref"
        }
      ]
    },
    {
      "DOI": "10.13039/100000002",
      "name": "National Institutes of Health",
      "doi-asserted-by": "crossref",
      "award": [
        "R01 AI093967"
      ],
      "id": [
        {
          "id": "10.13039/100000002",
          "id-type": "DOI",
          "asserted-by": "crossref"
        }
      ]
    },
    {
      "DOI": "10.13039/100000011",
      "name": "Howard Hughes Medical Institute",
      "doi-asserted-by": "crossref",
      "id": [
        {
          "id": "10.13039/100000011",
          "id-type": "DOI",
          "asserted-by": "crossref"
        }
      ]
    },
    {
      "DOI": "10.13039/100000002",
      "name": "National Institutes of Health",
      "doi-asserted-by": "crossref",
      "award": [
        "C06RR30414"
      ],
      "id": [
        {
          "id": "10.13039/100000002",
          "id-type": "DOI",
          "asserted-by": "crossref"
        }
      ]
    },
    {
      "DOI": "10.13039/100000002",
      "name": "National Institutes of Health",
      "doi-asserted-by": "publisher",
      "award": [
        "R01 GM088745"
      ],
      "id": [
        {
          "id": "10.13039/100000002",
          "id-type": "DOI",
          "asserted-by": "publisher"
        }
      ]
    },
    {
      "DOI": "10.13039/100000002",
      "name": "National Institutes of Health",
      "doi-asserted-by": "publisher",
      "award": [
        "R01GM093271"
      ],
      "id": [
        {
          "id": "10.13039/100000002",
          "id-type": "DOI",
          "asserted-by": "publisher"
        }
      ]
    },
    {
      "DOI": "10.13039/100000002",
      "name": "National Institutes of Health",
      "doi-asserted-by": "publisher",
      "award": [
        "R01GM088197"
      ],
      "id": [
        {
          "id": "10.13039/100000002",
          "id-type": "DOI",
          "asserted-by": "publisher"
        }
      ]
    },
    {
      "DOI": "10.13039/100000002",
      "name": "National Institutes of Health",
      "doi-asserted-by": "publisher",
      "award": [
        "1S10RR027972"
      ],
      "id": [
        {
          "id": "10.13039/100000002",
          "id-type": "DOI",
          "asserted-by": "publisher"
        }
      ]
    },
    {
      "DOI": "10.13039/100000968",
      "name": "American Heart Association",
      "doi-asserted-by": "publisher",
      "award": [
        "12IRG9400019"
      ],
      "id": [
        {
          "id": "10.13039/100000968",
          "id-type": "DOI",
          "asserted-by": "publisher"
        }
      ]
    },
    {
      "DOI": "10.13039/100000928",
      "name": "Welch Foundation",
      "doi-asserted-by": "publisher",
      "award": [
        "I-1684, I-1389, and I-1702"
      ],
      "id": [
        {
          "id": "10.13039/100000928",
          "id-type": "DOI",
          "asserted-by": "publisher"
        }
      ]
    },
    {
      "DOI": "10.13039/100004917",
      "name": "Cancer Prevention and Research Institute of Texas",
      "doi-asserted-by": "publisher",
      "award": [
        "RP120474"
      ],
      "id": [
        {
          "id": "10.13039/100004917",
          "id-type": "DOI",
          "asserted-by": "publisher"
        }
      ]
    },
    {
      "DOI": "10.13039/100000002",
      "name": "National Institutes of Health",
      "doi-asserted-by": "publisher",
      "award": [
        "R01 AI093967"
      ],
      "id": [
        {
          "id": "10.13039/100000002",
          "id-type": "DOI",
          "asserted-by": "publisher"
        }
      ]
    },
    {
      "DOI": "10.13039/100000011",
      "name": "Howard Hughes Medical Institute",
      "doi-asserted-by": "publisher",
      "id": [
        {
          "id": "10.13039/100000011",
          "id-type": "DOI",
          "asserted-by": "publisher"
        }
      ]
    },
    {
      "DOI": "10.13039/100000002",
      "name": "National Institutes of Health",
      "doi-asserted-by": "publisher",
      "award": [
        "C06RR30414"
      ],
      "id": [
        {
          "id": "10.13039/100000002",
          "id-type": "DOI",
          "asserted-by": "publisher"
        }
      ]
    }
  ],
  "content-domain": {
    "domain": [
      "www.elifesciences.org"
    ],
    "crossmark-restriction": false
  },
  "abstract": "<jats:p>Mitochondrial antiviral signaling (MAVS) protein is required for innate immune responses against RNA viruses. In virus-infected cells MAVS forms prion-like aggregates to activate antiviral signaling cascades, but the underlying structural mechanism is unknown. Here we report cryo-electron microscopic structures of the helical filaments formed by both the N-terminal caspase activation and recruitment domain (CARD) of MAVS and a truncated MAVS lacking part of the proline-rich region and the C-terminal transmembrane domain. Both structures are left-handed three-stranded helical filaments, revealing specific interfaces between individual CARD subunits that are dictated by electrostatic interactions between neighboring strands and hydrophobic interactions within each strand. Point mutations at multiple locations of these two interfaces impaired filament formation and antiviral signaling. Super-resolution imaging of virus-infected cells revealed rod-shaped MAVS clusters on mitochondria. These results elucidate the structural mechanism of MAVS polymerization, and explain how an \u03b1-helical domain uses distinct chemical interactions to form self-perpetuating filaments.</jats:p>",
  "DOI": "10.7554/elife.01489",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2014,
        2,
        25
      ]
    ],
    "date-time": "2014-02-25T16:23:16Z",
    "timestamp": 1393345396000
  },
  "source": "Crossref",
  "is-referenced-by-count": 152,
  "title": "Structural basis for the prion-like MAVS filaments in antiviral innate immunity",
  "prefix": "10.7554",
  "volume": "3",
  "author": [
    {
      "given": "Hui",
      "family": "Xu",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States"
        },
        {
          "name": "Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States"
        }
      ]
    },
    {
      "given": "Xiaojing",
      "family": "He",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States"
        }
      ]
    },
    {
      "given": "Hui",
      "family": "Zheng",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States"
        }
      ]
    },
    {
      "given": "Lily J",
      "family": "Huang",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States"
        }
      ]
    },
    {
      "given": "Fajian",
      "family": "Hou",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States"
        }
      ]
    },
    {
      "given": "Zhiheng",
      "family": "Yu",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "CryoEM Shared Resources, Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, United States"
        }
      ]
    },
    {
      "given": "Michael Jason",
      "family": "de la Cruz",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "CryoEM Shared Resources, Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, United States"
        }
      ]
    },
    {
      "given": "Brian",
      "family": "Borkowski",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States"
        }
      ]
    },
    {
      "given": "Xuewu",
      "family": "Zhang",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States"
        },
        {
          "name": "Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States"
        }
      ]
    },
    {
      "given": "Zhijian J",
      "family": "Chen",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Molecular Biology, Howard Hughes Medical Institute, University of Texas Southwestern Medical School, Dallas, United States"
        }
      ]
    },
    {
      "given": "Qiu-Xing",
      "family": "Jiang",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States"
        }
      ]
    }
  ],
  "member": "4374",
  "published-online": {
    "date-parts": [
      [
        2014,
        2,
        25
      ]
    ]
  },
  "reference": [
    {
      "key": "bib1",
      "doi-asserted-by": "publisher",
      "first-page": "1948",
      "DOI": "10.1107/S0907444902016657",
      "article-title": "PHENIX: building new software for automated crystallographic structure determination",
      "volume": "58",
      "author": "Adams",
      "year": "2002",
      "journal-title": "Acta Crystallographica Section D Biological Crystallography"
    },
    {
      "key": "bib2",
      "doi-asserted-by": "publisher",
      "first-page": "1714",
      "DOI": "10.1038/emboj.2012.19",
      "article-title": "MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA",
      "volume": "31",
      "author": "Berke",
      "year": "2012",
      "journal-title": "The EMBO Journal"
    },
    {
      "key": "bib3",
      "doi-asserted-by": "publisher",
      "first-page": "133",
      "DOI": "10.1038/embor.2009.258",
      "article-title": "Mitochondrial dynamics regulate the RIG-I-like receptor antiviral pathway",
      "volume": "11",
      "author": "Castanier",
      "year": "2010",
      "journal-title": "EMBO Reports"
    },
    {
      "key": "bib4",
      "doi-asserted-by": "publisher",
      "first-page": "1127",
      "DOI": "10.1038/embor.2011.190",
      "article-title": "The RIG-I ATPase domain structure reveals insights into ATP-dependent antiviral signalling",
      "volume": "12",
      "author": "Civril",
      "year": "2011",
      "journal-title": "EMBO Reports"
    },
    {
      "key": "bib5",
      "doi-asserted-by": "publisher",
      "first-page": "83",
      "DOI": "10.1016/j.jsb.2006.05.015",
      "article-title": "The iterative helical real space reconstruction method: surmounting the problems posed by real polymers",
      "volume": "157",
      "author": "Egelman",
      "year": "2007",
      "journal-title": "Journal of Structural Biology"
    },
    {
      "key": "bib6",
      "doi-asserted-by": "publisher",
      "first-page": "2126",
      "DOI": "10.1107/S0907444904019158",
      "article-title": "Coot: model-building tools for molecular graphics",
      "volume": "60",
      "author": "Emsley",
      "year": "2004",
      "journal-title": "Acta Crystallographica Section D Biological Crystallography"
    },
    {
      "key": "bib7",
      "doi-asserted-by": "publisher",
      "first-page": "486",
      "DOI": "10.1107/S0907444910007493",
      "article-title": "Features and development of Coot",
      "volume": "66",
      "author": "Emsley",
      "year": "2010",
      "journal-title": "Acta Crystallographica Section D Biological Crystallography"
    },
    {
      "key": "bib8",
      "doi-asserted-by": "publisher",
      "first-page": "313",
      "DOI": "10.1016/j.sbi.2010.03.011",
      "article-title": "SF1 and SF2 helicases: family matters",
      "volume": "20",
      "author": "Fairman-Williams",
      "year": "2010",
      "journal-title": "Current Opinion in Structural Biology"
    },
    {
      "key": "bib9",
      "doi-asserted-by": "crossref",
      "DOI": "10.1093/acprof:oso/9780195182187.001.0001",
      "volume-title": "Three-dimensional electron microscopy of macromolecular assemblies",
      "author": "Frank",
      "year": "2006"
    },
    {
      "key": "bib10",
      "doi-asserted-by": "publisher",
      "first-page": "4",
      "DOI": "10.1016/j.immuni.2009.06.014",
      "article-title": "A nonself RNA pattern: tri-p to panhandle",
      "volume": "31",
      "author": "Fujita",
      "year": "2009",
      "journal-title": "Immunity"
    },
    {
      "key": "bib11",
      "doi-asserted-by": "publisher",
      "first-page": "104",
      "DOI": "10.1016/j.it.2010.12.005",
      "article-title": "What the Myddosome structure tells us about the initiation of innate immunity",
      "volume": "32",
      "author": "Gay",
      "year": "2011",
      "journal-title": "Trends in immunology"
    },
    {
      "key": "bib12",
      "doi-asserted-by": "publisher",
      "first-page": "4957",
      "DOI": "10.1529/biophysj.107.120345",
      "article-title": "Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination",
      "volume": "94",
      "author": "Gustafsson",
      "year": "2008",
      "journal-title": "Biophysical Journal"
    },
    {
      "key": "bib13",
      "doi-asserted-by": "publisher",
      "first-page": "380",
      "DOI": "10.1016/j.str.2007.12.017",
      "article-title": "Regulation of enzyme localization by polymerization: polymer formation by the SAM domain of diacylglycerol kinase delta1",
      "volume": "16",
      "author": "Harada",
      "year": "2008",
      "journal-title": "Structure"
    },
    {
      "key": "bib14",
      "doi-asserted-by": "publisher",
      "first-page": "15610",
      "DOI": "10.1073/pnas.0906923106",
      "article-title": "Crystal structure of the plexin A3 intracellular region reveals an autoinhibited conformation through active site sequestration",
      "volume": "106",
      "author": "He",
      "year": "2009",
      "journal-title": "Proceedings of the National Academy of Sciences of the United States of America"
    },
    {
      "key": "bib15",
      "doi-asserted-by": "publisher",
      "first-page": "401",
      "DOI": "10.1039/c0nr00615g",
      "article-title": "Two-layer membranes of calcium phosphate/collagen/PLGA nanofibres: in vitro biomineralisation and osteogenic differentiation of human mesenchymal stem cells",
      "volume": "3",
      "author": "Hild",
      "year": "2011",
      "journal-title": "Nanoscale"
    },
    {
      "key": "bib16",
      "doi-asserted-by": "publisher",
      "first-page": "994",
      "DOI": "10.1126/science.1132505",
      "article-title": "5\u2019-Triphosphate RNA is the ligand for RIG-I",
      "volume": "314",
      "author": "Hornung",
      "year": "2006",
      "journal-title": "Science"
    },
    {
      "key": "bib17",
      "doi-asserted-by": "publisher",
      "first-page": "448",
      "DOI": "10.1016/j.cell.2011.06.041",
      "article-title": "MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response",
      "volume": "146",
      "author": "Hou",
      "year": "2011",
      "journal-title": "Cell"
    },
    {
      "key": "bib18",
      "doi-asserted-by": "publisher",
      "first-page": "291",
      "DOI": "10.1126/science.1183021",
      "article-title": "Regulation of adaptive immunity by the innate immune system",
      "volume": "327",
      "author": "Iwasaki",
      "year": "2010",
      "journal-title": "Science"
    },
    {
      "key": "bib19",
      "doi-asserted-by": "publisher",
      "first-page": "111",
      "DOI": "10.1007/978-1-61779-166-6_9",
      "article-title": "Electron microscopic imaging of integrin",
      "volume": "757",
      "author": "Iwasaki",
      "year": "2012",
      "journal-title": "Methods in Molecular Biology"
    },
    {
      "key": "bib20",
      "doi-asserted-by": "publisher",
      "first-page": "423",
      "DOI": "10.1038/nature10537",
      "article-title": "Structural basis of RNA recognition and activation by innate immune receptor RIG-I",
      "volume": "479",
      "author": "Jiang",
      "year": "2011",
      "journal-title": "Nature"
    },
    {
      "key": "bib21",
      "doi-asserted-by": "publisher",
      "first-page": "959",
      "DOI": "10.1016/j.immuni.2012.03.022",
      "article-title": "Ubiquitin-induced oligomerization of the RNA sensors RIG-I and MDA5 activates antiviral innate immune response",
      "volume": "36",
      "author": "Jiang",
      "year": "2012",
      "journal-title": "Immunity"
    },
    {
      "key": "bib22",
      "doi-asserted-by": "publisher",
      "first-page": "1601",
      "DOI": "10.1084/jem.20080091",
      "article-title": "Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5",
      "volume": "205",
      "author": "Kato",
      "year": "2008",
      "journal-title": "The Journal of Experimental Medicine"
    },
    {
      "key": "bib23",
      "first-page": "1231",
      "article-title": "[Role of IPS-1 in type I IFN induction]",
      "volume": "64",
      "author": "Kawai",
      "year": "2006",
      "journal-title": "Nihon Rinsho Japanese Journal of Clinical Medicine"
    },
    {
      "key": "bib24",
      "doi-asserted-by": "publisher",
      "first-page": "981",
      "DOI": "10.1038/ni1243",
      "article-title": "IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction",
      "volume": "6",
      "author": "Kawai",
      "year": "2005",
      "journal-title": "Nature Immunology"
    },
    {
      "key": "bib25",
      "doi-asserted-by": "publisher",
      "first-page": "541",
      "DOI": "10.1016/j.tibs.2011.06.006",
      "article-title": "The death-fold superfamily of homotypic interaction motifs",
      "volume": "36",
      "author": "Kersse",
      "year": "2011",
      "journal-title": "Trends in Biochemical Sciences"
    },
    {
      "key": "bib26",
      "doi-asserted-by": "publisher",
      "first-page": "772",
      "DOI": "10.1038/embor.2013.108",
      "article-title": "Defining the functional determinants for RNA surveillance by RIG-I",
      "volume": "14",
      "author": "Kohlway",
      "year": "2013",
      "journal-title": "EMBO Reports"
    },
    {
      "key": "bib27",
      "doi-asserted-by": "publisher",
      "first-page": "ra7",
      "DOI": "10.1126/scisignal.2001147",
      "article-title": "Mitochondrial membrane potential is required for MAVS-mediated antiviral signaling",
      "volume": "4",
      "author": "Koshiba",
      "year": "2011",
      "journal-title": "Science signaling"
    },
    {
      "key": "bib28",
      "doi-asserted-by": "publisher",
      "first-page": "423",
      "DOI": "10.1016/j.cell.2011.09.039",
      "article-title": "Structural basis for the activation of innate immune pattern-recognition receptor RIG-i by viral RNA",
      "volume": "147",
      "author": "Kowalinski",
      "year": "2011",
      "journal-title": "Cell"
    },
    {
      "key": "bib29",
      "doi-asserted-by": "publisher",
      "first-page": "2191",
      "DOI": "10.1099/vir.0.032367-0",
      "article-title": "RNA helicase retinoic acid-inducible gene I as a sensor of Hantaan virus replication",
      "volume": "92",
      "author": "Lee",
      "year": "2011",
      "journal-title": "The Journal of General Virology"
    },
    {
      "key": "bib30",
      "doi-asserted-by": "publisher",
      "first-page": "885",
      "DOI": "10.1038/nature09121",
      "article-title": "Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling",
      "volume": "465",
      "author": "Lin",
      "year": "2010",
      "journal-title": "Nature"
    },
    {
      "key": "bib31",
      "doi-asserted-by": "publisher",
      "first-page": "e00785",
      "DOI": "10.7554/eLife.00785",
      "article-title": "MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades",
      "volume": "2",
      "author": "Liu",
      "year": "2013",
      "journal-title": "eLife"
    },
    {
      "key": "bib32",
      "doi-asserted-by": "publisher",
      "first-page": "335",
      "DOI": "10.1128/JVI.01080-07",
      "article-title": "Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity",
      "volume": "82",
      "author": "Loo",
      "year": "2008",
      "journal-title": "Journal of Virology"
    },
    {
      "key": "bib33",
      "doi-asserted-by": "publisher",
      "first-page": "82",
      "DOI": "10.1006/jsbi.1999.4174",
      "article-title": "EMAN: semiautomated software for high-resolution single-particle reconstructions",
      "volume": "128",
      "author": "Ludtke",
      "year": "1999",
      "journal-title": "Journal of Structural Biology"
    },
    {
      "key": "bib34",
      "doi-asserted-by": "publisher",
      "first-page": "409",
      "DOI": "10.1016/j.cell.2011.09.023",
      "article-title": "Structural insights into RNA recognition by RIG-I",
      "volume": "147",
      "author": "Luo",
      "year": "2011",
      "journal-title": "Cell"
    },
    {
      "key": "bib35",
      "doi-asserted-by": "publisher",
      "first-page": "111",
      "DOI": "10.4161/rna.22706",
      "article-title": "Duplex RNA activated ATPases (DRAs): platforms for RNA sensing, signaling and processing",
      "volume": "10",
      "author": "Luo",
      "year": "2013",
      "journal-title": "RNA Biology"
    },
    {
      "key": "bib36",
      "doi-asserted-by": "publisher",
      "first-page": "1983",
      "DOI": "10.1016/j.str.2012.08.029",
      "article-title": "Visualizing the determinants of viral RNA recognition by innate immune sensor RIG-I",
      "volume": "20",
      "author": "Luo",
      "year": "2012",
      "journal-title": "Structure"
    },
    {
      "key": "bib37",
      "doi-asserted-by": "publisher",
      "first-page": "6108",
      "DOI": "10.1074/jbc.M110.186262",
      "article-title": "Short double-stranded RNAs with an overhanging 5\u2019 ppp-nucleotide, as found in arenavirus genomes, act as RIG-I decoys",
      "volume": "286",
      "author": "Marq",
      "year": "2011",
      "journal-title": "The Journal of Biological Chemistry"
    },
    {
      "key": "bib38",
      "doi-asserted-by": "publisher",
      "first-page": "658",
      "DOI": "10.1107/S0021889807021206",
      "article-title": "Phaser crystallographic software",
      "volume": "40",
      "author": "McCoy",
      "year": "2007",
      "journal-title": "Journal of Applied Crystallography"
    },
    {
      "key": "bib39",
      "doi-asserted-by": "publisher",
      "first-page": "1167",
      "DOI": "10.1038/nature04193",
      "article-title": "Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus",
      "volume": "437",
      "author": "Meylan",
      "year": "2005",
      "journal-title": "Nature"
    },
    {
      "key": "bib40",
      "doi-asserted-by": "publisher",
      "first-page": "11910",
      "DOI": "10.1073/pnas.97.22.11910",
      "article-title": "A census of glutamine/asparagine-rich regions: implications for their conserved function and the prediction of novel prions",
      "volume": "97",
      "author": "Michelitsch",
      "year": "2000",
      "journal-title": "Proceedings of the National Academy of Sciences of the United States of America"
    },
    {
      "key": "bib41",
      "doi-asserted-by": "publisher",
      "first-page": "103",
      "DOI": "10.1038/nature12729",
      "article-title": "Antibacterial membrane attack by a pore-forming intestinal C-type lectin",
      "volume": "505",
      "author": "Mukherjee",
      "year": "2014",
      "journal-title": "Nature"
    },
    {
      "key": "bib42",
      "doi-asserted-by": "publisher",
      "first-page": "15825",
      "DOI": "10.1074/jbc.M800542200",
      "article-title": "Structure and function of LGP2, a DEX(D/H) helicase that regulates the innate immunity response",
      "volume": "283",
      "author": "Murali",
      "year": "2008",
      "journal-title": "The Journal of Biological Chemistry"
    },
    {
      "key": "bib43",
      "doi-asserted-by": "publisher",
      "first-page": "443",
      "DOI": "10.1146/annurev-biophys-083012-130338",
      "article-title": "Molecular basis of NF-kappaB signaling",
      "volume": "42",
      "author": "Napetschnig",
      "year": "2013",
      "journal-title": "Annual Review of Biophysics"
    },
    {
      "key": "bib44",
      "doi-asserted-by": "publisher",
      "first-page": "773",
      "DOI": "10.1038/nature03680",
      "article-title": "Structure of the cross-beta spine of amyloid-like fibrils",
      "volume": "435",
      "author": "Nelson",
      "year": "2005",
      "journal-title": "Nature"
    },
    {
      "key": "bib45",
      "doi-asserted-by": "publisher",
      "first-page": "10395",
      "DOI": "10.1073/pnas.97.19.10395",
      "article-title": "Molecular basis for CD40 signaling mediated by TRAF3",
      "volume": "97",
      "author": "Ni",
      "year": "2000",
      "journal-title": "Proceedings of the National Academy of Sciences of the United States of America"
    },
    {
      "key": "bib46",
      "doi-asserted-by": "publisher",
      "first-page": "e1001012",
      "DOI": "10.1371/journal.ppat.1001012",
      "article-title": "Virus-infection or 5\u2019ppp-RNA activates antiviral signal through redistribution of IPS-1 mediated by MFN1",
      "volume": "6",
      "author": "Onoguchi",
      "year": "2010",
      "journal-title": "PLoS Pathogens"
    },
    {
      "key": "bib47",
      "doi-asserted-by": "publisher",
      "first-page": "307",
      "DOI": "10.1016/S0076-6879(97)76066-X",
      "article-title": "Processing of X-ray diffraction data collected in oscillation mode",
      "volume": "276",
      "author": "Otwinowski",
      "year": "1997",
      "journal-title": "Methods in Enzymology"
    },
    {
      "key": "bib48",
      "doi-asserted-by": "publisher",
      "first-page": "533",
      "DOI": "10.1038/19110",
      "article-title": "Structural basis for self-association and receptor recognition of human TRAF2",
      "volume": "398",
      "author": "Park",
      "year": "1999",
      "journal-title": "Nature"
    },
    {
      "key": "bib49",
      "doi-asserted-by": "publisher",
      "first-page": "780",
      "DOI": "10.1038/embor.2013.102",
      "article-title": "ATPase-driven oligomerization of RIG-I on RNA allows optimal activation of type-I interferon",
      "volume": "14",
      "author": "Patel",
      "year": "2013",
      "journal-title": "EMBO Reports"
    },
    {
      "key": "bib50",
      "doi-asserted-by": "publisher",
      "first-page": "21010",
      "DOI": "10.1073/pnas.1113651108",
      "article-title": "Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition",
      "volume": "108",
      "author": "Peisley",
      "year": "2011",
      "journal-title": "Proceedings of the National Academy of Sciences of the United States of America"
    },
    {
      "key": "bib51",
      "doi-asserted-by": "publisher",
      "first-page": "573",
      "DOI": "10.1016/j.molcel.2013.07.024",
      "article-title": "RIG-I forms signaling-competent filaments in an ATP-dependent, ubiquitin-independent manner",
      "volume": "51",
      "author": "Peisley",
      "year": "2013",
      "journal-title": "Molecular Cell"
    },
    {
      "key": "bib52",
      "doi-asserted-by": "publisher",
      "first-page": "1605",
      "DOI": "10.1002/jcc.20084",
      "article-title": "UCSF Chimera\u2013a visualization system for exploratory research and analysis",
      "volume": "25",
      "author": "Pettersen",
      "year": "2004",
      "journal-title": "Journal of Computational Chemistry"
    },
    {
      "key": "bib53",
      "doi-asserted-by": "publisher",
      "first-page": "11",
      "DOI": "10.1186/1472-6807-8-11",
      "article-title": "Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain",
      "volume": "8",
      "author": "Potter",
      "year": "2008",
      "journal-title": "BMC Structural Biology"
    },
    {
      "key": "bib54",
      "doi-asserted-by": "publisher",
      "first-page": "1155",
      "DOI": "10.1074/jbc.M806219200",
      "article-title": "Agonist and antagonist recognition by RIG-I, a cytoplasmic innate immunity receptor",
      "volume": "284",
      "author": "Ranjith-Kumar",
      "year": "2009",
      "journal-title": "The Journal of Biological Chemistry"
    },
    {
      "key": "bib55",
      "doi-asserted-by": "publisher",
      "first-page": "1061",
      "DOI": "10.1126/science.1189468",
      "article-title": "Plant and animal sensors of conserved microbial signatures",
      "volume": "330",
      "author": "Ronald",
      "year": "2010",
      "journal-title": "Science"
    },
    {
      "key": "bib56",
      "doi-asserted-by": "publisher",
      "first-page": "25",
      "DOI": "10.1016/j.immuni.2009.05.008",
      "article-title": "Recognition of 5\u2019 triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus",
      "volume": "31",
      "author": "Schlee",
      "year": "2009",
      "journal-title": "Immunity"
    },
    {
      "key": "bib57",
      "doi-asserted-by": "publisher",
      "first-page": "669",
      "DOI": "10.1016/j.cell.2005.08.012",
      "article-title": "Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3",
      "volume": "122",
      "author": "Seth",
      "year": "2005",
      "journal-title": "Cell"
    },
    {
      "key": "bib58",
      "doi-asserted-by": "publisher",
      "first-page": "805",
      "DOI": "10.1016/j.cell.2010.01.022",
      "article-title": "Pattern recognition receptors and inflammation",
      "volume": "140",
      "author": "Takeuchi",
      "year": "2010",
      "journal-title": "Cell"
    },
    {
      "key": "bib59",
      "doi-asserted-by": "publisher",
      "first-page": "21",
      "DOI": "10.1007/s12551-009-0026-3",
      "article-title": "Using Situs for the integration of multi-resolution structures",
      "volume": "2",
      "author": "Wriggers",
      "year": "2010",
      "journal-title": "Biophysical Reviews"
    },
    {
      "key": "bib60",
      "doi-asserted-by": "publisher",
      "first-page": "276",
      "DOI": "10.1016/j.cell.2012.11.048",
      "article-title": "Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5",
      "volume": "152",
      "author": "Wu",
      "year": "2013",
      "journal-title": "Cell"
    },
    {
      "key": "bib61",
      "doi-asserted-by": "publisher",
      "first-page": "727",
      "DOI": "10.1016/j.molcel.2005.08.014",
      "article-title": "VISA is an adapter protein required for virus-triggered IFN-beta signaling",
      "volume": "19",
      "author": "Xu",
      "year": "2005",
      "journal-title": "Molecular Cell"
    },
    {
      "key": "bib62",
      "doi-asserted-by": "publisher",
      "first-page": "ra47",
      "DOI": "10.1126/scisignal.2000287",
      "article-title": "Mitofusin 2 inhibits mitochondrial antiviral signaling",
      "volume": "2",
      "author": "Yasukawa",
      "year": "2009",
      "journal-title": "Science signaling"
    },
    {
      "key": "bib63",
      "doi-asserted-by": "publisher",
      "first-page": "54",
      "DOI": "10.1111/j.1600-065X.2008.00727.x",
      "article-title": "RNA recognition and signal transduction by RIG-I-like receptors",
      "volume": "227",
      "author": "Yoneyama",
      "year": "2009",
      "journal-title": "Immunological Review"
    },
    {
      "key": "bib64",
      "doi-asserted-by": "publisher",
      "first-page": "730",
      "DOI": "10.1038/ni1087",
      "article-title": "The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses",
      "volume": "5",
      "author": "Yoneyama",
      "year": "2004",
      "journal-title": "Nature Immunology"
    },
    {
      "key": "bib65",
      "doi-asserted-by": "publisher",
      "first-page": "112",
      "DOI": "10.1016/j.jmb.2012.10.006",
      "article-title": "Unclosed HIV-1 capsids suggest a curled sheet model of assembly",
      "volume": "425",
      "author": "Yu",
      "year": "2013",
      "journal-title": "Journal of Molecular Biology"
    },
    {
      "key": "bib66",
      "doi-asserted-by": "publisher",
      "first-page": "315",
      "DOI": "10.1016/j.cell.2010.03.029",
      "article-title": "Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity",
      "volume": "141",
      "author": "Zeng",
      "year": "2010",
      "journal-title": "Cell"
    },
    {
      "key": "bib67",
      "doi-asserted-by": "publisher",
      "first-page": "101",
      "DOI": "10.1016/j.molcel.2010.03.009",
      "article-title": "Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: affinity, specificity, and regulation",
      "volume": "38",
      "author": "Zheng",
      "year": "2010",
      "journal-title": "Molecular Cell"
    }
  ],
  "updated-by": [
    {
      "updated": {
        "date-parts": [
          [
            2015,
            8,
            28
          ]
        ],
        "date-time": "2015-08-28T00:00:00Z",
        "timestamp": 1440720000000
      },
      "DOI": "10.7554/elife.07546",
      "type": "correction",
      "source": "publisher",
      "label": "Correction"
    }
  ],
  "container-title": "eLife",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://cdn.elifesciences.org/articles/01489/elife-01489-v1.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://cdn.elifesciences.org/articles/01489/elife-01489-v1.xml",
      "content-type": "application/xml",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://elifesciences.org/articles/01489",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        10,
        12
      ]
    ],
    "date-time": "2023-10-12T00:43:10Z",
    "timestamp": 1697071390000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://elifesciences.org/articles/01489"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2014,
        2,
        25
      ]
    ]
  },
  "references-count": 67,
  "alternative-id": [
    "10.7554/eLife.01489"
  ],
  "URL": "http://dx.doi.org/10.7554/eLife.01489",
  "relation": {
    "references": [
      {
        "id-type": "accession",
        "id": "2VGQ",
        "asserted-by": "subject"
      }
    ],
    "is-supplemented-by": [
      {
        "id-type": "accession",
        "id": "4O9L",
        "asserted-by": "subject"
      },
      {
        "id-type": "accession",
        "id": "4O9F",
        "asserted-by": "subject"
      },
      {
        "id-type": "accession",
        "id": "EMD-5890",
        "asserted-by": "subject"
      },
      {
        "id-type": "accession",
        "id": "EMD-5891",
        "asserted-by": "subject"
      },
      {
        "id-type": "accession",
        "id": "3J6C",
        "asserted-by": "subject"
      }
    ],
    "has-review": [
      {
        "id-type": "doi",
        "id": "10.7554/eLife.01489.020",
        "asserted-by": "object"
      },
      {
        "id-type": "doi",
        "id": "10.7554/eLife.01489.021",
        "asserted-by": "object"
      }
    ]
  },
  "ISSN": [
    "2050-084X"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2014,
        2,
        25
      ]
    ]
  },
  "assertion": [
    {
      "value": "2013-09-08",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2014-01-18",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2014-02-25",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ],
  "article-number": "e01489"
}