DOI: 10.1073/pnas.1113651108. Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition

Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition

10.1073/pnas.1113651108

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

MDA5, an RIG-I-like helicase, is a conserved cytoplasmic viral RNA sensor, which recognizes dsRNA from a wide-range of viruses in a length-dependent manner. It has been proposed that MDA5 forms higher-order structures upon viral dsRNA recognition or during antiviral signaling, however the organization and nature of this proposed oligomeric state is unknown. We report here that MDA5 cooperatively assembles into a filamentous oligomer composed of a repeating segmental arrangement of MDA5 dimers along the length of dsRNA. Binding of MDA5 to dsRNA stimulates its ATP hydrolysis activity with little coordination between neighboring molecules within a filament. Individual ATP hydrolysis in turn renders an intrinsic kinetic instability to the MDA5 filament, triggering dissociation of MDA5 from dsRNA at a rate inversely proportional to the filament length. These results suggest a previously unrecognized role of ATP hydrolysis in control of filament assembly and disassembly processes, thereby autoregulating the interaction of MDA5 with dsRNA, and provides a potential basis for dsRNA length-dependent antiviral signaling.

Bibliography

Peisley, A., Lin, C., Wu, B., Orme-Johnson, M., Liu, M., Walz, T., & Hur, S. (2011). Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition. Proceedings of the National Academy of Sciences, 108(52), 21010â21015.

Authors 7

Alys Peisley (first)
Cecilie Lin (additional)
Bin Wu (additional)
McGhee Orme-Johnson (additional)
Mengyuan Liu (additional)
Thomas Walz (additional)
Sun Hur (additional)

References 30 Referenced 263

Dates

Type	When
Created	13 years, 8 months ago (Dec. 13, 2011, 12:15 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 8:41 p.m.)
Indexed	2 weeks, 1 day ago (Aug. 6, 2025, 9:21 a.m.)
Issued	13 years, 8 months ago (Dec. 12, 2011)
Published	13 years, 8 months ago (Dec. 12, 2011)
Published Online	13 years, 8 months ago (Dec. 12, 2011)
Published Print	13 years, 7 months ago (Dec. 27, 2011)

Funders 0

None

BibTeX

@article{Peisley_2011, title={Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition}, volume={108}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1113651108}, DOI={10.1073/pnas.1113651108}, number={52}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Peisley, Alys and Lin, Cecilie and Wu, Bin and Orme-Johnson, McGhee and Liu, Mengyuan and Walz, Thomas and Hur, Sun}, year={2011}, month=dec, pages={21010–21015} }

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