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The architecture of respiratory complex I

Nature volume 465, pages 441445 (27 May 2010) | Download Citation

Abstract

Complex I is the first enzyme of the respiratory chain and has a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation by an unknown mechanism. Dysfunction of complex I has been implicated in many human neurodegenerative diseases. We have determined the structure of its hydrophilic domain previously. Here, we report the α-helical structure of the membrane domain of complex I from Escherichia coli at 3.9 Å resolution. The antiporter-like subunits NuoL/M/N each contain 14 conserved transmembrane (TM) helices. Two of them are discontinuous, as in some transporters. Unexpectedly, subunit NuoL also contains a 110-Å long amphipathic α-helix, spanning almost the entire length of the domain. Furthermore, we have determined the structure of the entire complex I from Thermus thermophilus at 4.5 Å resolution. The L-shaped assembly consists of the α-helical model for the membrane domain, with 63 TM helices, and the known structure of the hydrophilic domain. The architecture of the complex provides strong clues about the coupling mechanism: the conformational changes at the interface of the two main domains may drive the long amphipathic α-helix of NuoL in a piston-like motion, tilting nearby discontinuous TM helices, resulting in proton translocation.

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Data deposits

The coordinates and structure factors have been deposited in the RCSB Protein Data Bank under accession codes 3M9C (membrane domain of complex I from E. coli) and 3M9S (intact complex I from T. thermophilus).

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Acknowledgements

This work was funded by the Medical Research Council. We thank the European Synchrotron Radiation Facility and the Swiss Light Source for provision of synchrotron radiation facilities. We are grateful to the staff of beamlines ID23, ID29 (ESRF, Grenoble) and X06SA (Swiss Light Source, Villigen) for assistance. We thank J. E. Walker and A. Leslie for discussions of the manuscript.

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Affiliations

  1. Medical Research Council Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK

    • Rouslan G. Efremov
    • , Rozbeh Baradaran
    •  & Leonid A. Sazanov

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Contributions

R.G.E. purified and crystallized the membrane domain of E. coli complex I; R.B. purified and crystallized intact T. thermophilus complex I; R.G.E. and R.B. collected and analysed X-ray data; L.A.S. designed the project, analysed data and wrote the manuscript, with contributions from R.G.E. and R.B.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Leonid A. Sazanov.

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    Supplementary information

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https://doi.org/10.1038/nature09066

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