DOI: 10.1126/science.1123809. Structure of the Hydrophilic Domain of Respiratory Complex I from <i>Thermus thermophilus</i>

Structure of the Hydrophilic Domain of Respiratory Complex I from Thermus thermophilus

10.1126/science.1123809

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Respiratory complex I plays a central role in cellular energy production in bacteria and mitochondria. Its dysfunction is implicated in many human neurodegenerative diseases, as well as in aging. The crystal structure of the hydrophilic domain (peripheral arm) of complex I from Thermus thermophilus has been solved at 3.3 angstrom resolution. This subcomplex consists of eight subunits and contains all the redox centers of the enzyme, including nine iron-sulfur clusters. The primary electron acceptor, flavin-mononucleotide, is within electron transfer distance of cluster N3, leading to the main redox pathway, and of the distal cluster N1a, a possible antioxidant. The structure reveals new aspects of the mechanism and evolution of the enzyme. The terminal cluster N2 is coordinated, uniquely, by two consecutive cysteines. The novel subunit Nqo15 has a similar fold to the mitochondrial iron chaperone frataxin, and it may be involved in iron-sulfur cluster regeneration in the complex.

Bibliography

Sazanov, L. A., & Hinchliffe, P. (2006). Structure of the Hydrophilic Domain of Respiratory Complex I from Thermus thermophilus. Science, 311(5766), 1430â1436.

Authors 2

Leonid A. Sazanov (first)
Philip Hinchliffe (additional)

References 53 Referenced 680

10.1017/S003358350000425X
10.1021/bi027158b
10.1074/mcp.M300014-MCP200
10.1006/jmbi.1998.1668
10.1021/bi026876v
10.1006/jmbi.1997.1518
10.1016/S0005-2728(98)00032-2
10.1016/j.cell.2005.02.001
10.1016/S0005-2728(98)00027-9
10.1021/bi00161a022
10.1074/jbc.M308247200
10.1016/S0014-5793(00)01867-6
10.1111/j.1432-1033.1995.tb20594.x
10.1074/jbc.M410377200
10.1126/science.1113988
P. Hinchliffe J. Carroll L. A. Sazanov in preparation.
Materials and methods are available as supporting material on Science Online.
10.1038/46972
D. J. Morgan L. A. Sazanov unpublished data.
10.1107/S0907444904026460
10.1126/science.273.5275.595
10.1016/0959-440X(95)80010-7
10.1016/S0022-2836(05)80134-2
10.1006/jmbi.2000.3871
10.1016/S0168-6445(01)00063-8
10.1038/nsb969
10.1073/pnas.042664399
10.1126/science.282.5395.1853
10.1074/jbc.M212275200
10.1021/bi049938l
10.1016/S0969-2126(99)80010-0
10.1016/S0005-2728(98)00022-X
10.1074/jbc.273.41.26349
10.1074/jbc.M401539200
10.1016/j.bbabio.2003.09.001
10.1038/373580a0
10.1074/jbc.M308967200
10.1074/jbc.M102296200
10.1021/bi048132i
10.1016/S0014-5793(98)00719-4
10.1074/jbc.M313180200
10.1073/pnas.160270897
10.1074/jbc.C000407200
10.1126/science.1098991
10.1074/jbc.C400107200
10.1021/bi00199a034
10.1016/0014-5793(90)80753-6
10.1074/jbc.M310341200
10.1074/jbc.M503936200
10.1023/A:1010722717257
10.1021/bi00181a018
10.1021/ja961465l
This work was funded by the Medical Research Council. We thank J. E. Walker A. G. W. Leslie and A. G. Murzin for helpful discussions of the manuscript; the European Synchrotron Radiation Facility for provision of synchrotron radiation facilities; and the staff of beamlines ID23 and ID29 for assistance. The coordinates and the structure factors have been deposited in the Protein Data Bank (accession code 2FUG).

Dates

Type	When
Created	19 years, 6 months ago (Feb. 9, 2006, 8:44 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 9:09 p.m.)
Indexed	1 day, 19 hours ago (Aug. 23, 2025, 1:02 a.m.)
Issued	19 years, 5 months ago (March 10, 2006)
Published	19 years, 5 months ago (March 10, 2006)
Published Print	19 years, 5 months ago (March 10, 2006)

Funders 0

None

BibTeX

@article{Sazanov_2006, title={Structure of the Hydrophilic Domain of Respiratory Complex I from Thermus thermophilus}, volume={311}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1123809}, DOI={10.1126/science.1123809}, number={5766}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Sazanov, Leonid A. and Hinchliffe, Philip}, year={2006}, month=mar, pages={1430–1436} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        23
      ]
    ],
    "date-time": "2025-08-23T05:02:05Z",
    "timestamp": 1755925325710
  },
  "reference-count": 53,
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "issue": "5766",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2006,
        3,
        10
      ]
    ]
  },
  "abstract": "<jats:p>\n            Respiratory complex I plays a central role in cellular energy production in bacteria and mitochondria. Its dysfunction is implicated in many human neurodegenerative diseases, as well as in aging. The crystal structure of the hydrophilic domain (peripheral arm) of complex I from\n            <jats:italic>Thermus thermophilus</jats:italic>\n            has been solved at 3.3 angstrom resolution. This subcomplex consists of eight subunits and contains all the redox centers of the enzyme, including nine iron-sulfur clusters. The primary electron acceptor, flavin-mononucleotide, is within electron transfer distance of cluster N3, leading to the main redox pathway, and of the distal cluster N1a, a possible antioxidant. The structure reveals new aspects of the mechanism and evolution of the enzyme. The terminal cluster N2 is coordinated, uniquely, by two consecutive cysteines. The novel subunit Nqo15 has a similar fold to the mitochondrial iron chaperone frataxin, and it may be involved in iron-sulfur cluster regeneration in the complex.\n          </jats:p>",
  "DOI": "10.1126/science.1123809",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2006,
        2,
        10
      ]
    ],
    "date-time": "2006-02-10T01:44:29Z",
    "timestamp": 1139535869000
  },
  "page": "1430-1436",
  "source": "Crossref",
  "is-referenced-by-count": 680,
  "title": "Structure of the Hydrophilic Domain of Respiratory Complex I from\n            <i>Thermus thermophilus</i>",
  "prefix": "10.1126",
  "volume": "311",
  "author": [
    {
      "given": "Leonid A.",
      "family": "Sazanov",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, U.K."
        }
      ]
    },
    {
      "given": "Philip",
      "family": "Hinchliffe",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, U.K."
        }
      ]
    }
  ],
  "member": "221",
  "reference": [
    {
      "key": "e_1_3_1_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1017/S003358350000425X"
    },
    {
      "key": "e_1_3_1_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi027158b"
    },
    {
      "key": "e_1_3_1_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/mcp.M300014-MCP200"
    },
    {
      "key": "e_1_3_1_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/jmbi.1998.1668"
    },
    {
      "key": "e_1_3_1_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi026876v"
    },
    {
      "key": "e_1_3_1_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/jmbi.1997.1518"
    },
    {
      "key": "e_1_3_1_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0005-2728(98)00032-2"
    },
    {
      "key": "e_1_3_1_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.cell.2005.02.001"
    },
    {
      "key": "e_1_3_1_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0005-2728(98)00027-9"
    },
    {
      "key": "e_1_3_1_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00161a022"
    },
    {
      "key": "e_1_3_1_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M308247200"
    },
    {
      "key": "e_1_3_1_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0014-5793(00)01867-6"
    },
    {
      "key": "e_1_3_1_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1432-1033.1995.tb20594.x"
    },
    {
      "key": "e_1_3_1_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M410377200"
    },
    {
      "key": "e_1_3_1_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1113988"
    },
    {
      "key": "e_1_3_1_17_2",
      "unstructured": "P. Hinchliffe J. Carroll L. A. Sazanov in preparation."
    },
    {
      "key": "e_1_3_1_18_2",
      "unstructured": "Materials and methods are available as supporting material on Science Online."
    },
    {
      "key": "e_1_3_1_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/46972"
    },
    {
      "key": "e_1_3_1_20_2",
      "unstructured": "D. J. Morgan L. A. Sazanov unpublished data."
    },
    {
      "key": "e_1_3_1_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1107/S0907444904026460"
    },
    {
      "key": "e_1_3_1_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.273.5275.595"
    },
    {
      "key": "e_1_3_1_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0959-440X(95)80010-7"
    },
    {
      "key": "e_1_3_1_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0022-2836(05)80134-2"
    },
    {
      "key": "e_1_3_1_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/jmbi.2000.3871"
    },
    {
      "key": "e_1_3_1_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0168-6445(01)00063-8"
    },
    {
      "key": "e_1_3_1_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nsb969"
    },
    {
      "key": "e_1_3_1_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.042664399"
    },
    {
      "key": "e_1_3_1_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.282.5395.1853"
    },
    {
      "key": "e_1_3_1_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M212275200"
    },
    {
      "key": "e_1_3_1_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi049938l"
    },
    {
      "key": "e_1_3_1_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0969-2126(99)80010-0"
    },
    {
      "key": "e_1_3_1_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0005-2728(98)00022-X"
    },
    {
      "key": "e_1_3_1_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.273.41.26349"
    },
    {
      "key": "e_1_3_1_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M401539200"
    },
    {
      "key": "e_1_3_1_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.bbabio.2003.09.001"
    },
    {
      "key": "e_1_3_1_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/373580a0"
    },
    {
      "key": "e_1_3_1_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M308967200"
    },
    {
      "key": "e_1_3_1_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M102296200"
    },
    {
      "key": "e_1_3_1_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi048132i"
    },
    {
      "key": "e_1_3_1_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0014-5793(98)00719-4"
    },
    {
      "key": "e_1_3_1_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M313180200"
    },
    {
      "key": "e_1_3_1_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.160270897"
    },
    {
      "key": "e_1_3_1_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.C000407200"
    },
    {
      "key": "e_1_3_1_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1098991"
    },
    {
      "key": "e_1_3_1_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.C400107200"
    },
    {
      "key": "e_1_3_1_47_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00199a034"
    },
    {
      "key": "e_1_3_1_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-5793(90)80753-6"
    },
    {
      "key": "e_1_3_1_49_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M310341200"
    },
    {
      "key": "e_1_3_1_50_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M503936200"
    },
    {
      "key": "e_1_3_1_51_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1023/A:1010722717257"
    },
    {
      "key": "e_1_3_1_52_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00181a018"
    },
    {
      "key": "e_1_3_1_53_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja961465l"
    },
    {
      "key": "e_1_3_1_54_2",
      "unstructured": "This work was funded by the Medical Research Council. We thank J. E. Walker A. G. W. Leslie and A. G. Murzin for helpful discussions of the manuscript; the European Synchrotron Radiation Facility for provision of synchrotron radiation facilities; and the staff of beamlines ID23 and ID29 for assistance. The coordinates and the structure factors have been deposited in the Protein Data Bank (accession code 2FUG)."
    }
  ],
  "container-title": "Science",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://www.science.org/doi/pdf/10.1126/science.1123809",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        1,
        10
      ]
    ],
    "date-time": "2024-01-10T02:09:48Z",
    "timestamp": 1704852588000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.science.org/doi/10.1126/science.1123809"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2006,
        3,
        10
      ]
    ]
  },
  "references-count": 53,
  "journal-issue": {
    "issue": "5766",
    "published-print": {
      "date-parts": [
        [
          2006,
          3,
          10
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1126/science.1123809"
  ],
  "URL": "http://dx.doi.org/10.1126/science.1123809",
  "relation": {
    "has-review": [
      {
        "id-type": "doi",
        "id": "10.3410/f.1031528.365699",
        "asserted-by": "object"
      }
    ]
  },
  "ISSN": [
    "0036-8075",
    "1095-9203"
  ],
  "subject": [],
  "container-title-short": "Science",
  "published": {
    "date-parts": [
      [
        2006,
        3,
        10
      ]
    ]
  }
}