The architecture of respiratory complex I.

TitleThe architecture of respiratory complex I.
Publication TypeJournal Article
Year of Publication2010
AuthorsEfremov, R. G., Baradaran R., and Sazanov L. A.
Date Published2010 May 27
KeywordsBenzoquinones, Binding Sites, Cell Membrane, Crystallography, X-Ray, Electron Transport Complex I, Escherichia coli, Models, Molecular, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Subunits, Structure-Activity Relationship, Thermus thermophilus

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 alpha-helical structure of the membrane domain of complex I from Escherichia coli at 3.9 A 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-A long amphipathic alpha-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 A resolution. The L-shaped assembly consists of the alpha-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 alpha-helix of NuoL in a piston-like motion, tilting nearby discontinuous TM helices, resulting in proton translocation.

Alternate JournalNature
PubMed ID20505720
Grant List / / Medical Research Council / United Kingdom
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