The coupling mechanism of respiratory complex I - a structural and evolutionary perspective.

TitleThe coupling mechanism of respiratory complex I - a structural and evolutionary perspective.
Publication TypeJournal Article
Year of Publication2012
AuthorsEfremov, R. G., and Sazanov L. A.
JournalBiochim Biophys Acta
Volume1817
Issue10
Pagination1785-95
Date Published2012 Oct
ISSN0006-3002
KeywordsBacteria, Bacterial Proteins, Electron Transport Complex I, Evolution, Molecular, Ion Transport, Protein Structure, Quaternary, Structural Homology, Protein, Structure-Activity Relationship
Abstract

Complex I is a key enzyme of the respiratory chain in many organisms. This multi-protein complex with an intricate evolutionary history originated from the unification of prebuilt modules of hydrogenases and transporters. Using recently determined crystallographic structures of complex I we reanalyzed evolutionarily related complexes that couple oxidoreduction to trans-membrane ion translocation. Our analysis points to the previously unnoticed structural homology of the electron input module of formate dehydrogenlyases and subunit NuoG of complex I. We also show that all related to complex I hydrogenases likely operate via a conformation driven mechanism with structural changes generated in the conserved coupling site located at the interface of subunits NuoB/D/H. The coupling apparently originated once in evolutionary history, together with subunit NuoH joining hydrogenase and transport modules. Analysis of quinone oxidoreduction properties and the structure of complex I allows us to suggest a fully reversible coupling mechanism. Our model predicts that: 1) proton access to the ketone groups of the bound quinone is rigorously controlled by the protein, 2) the negative electric charge of the anionic ubiquinol head group is a major driving force for conformational changes. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).

DOI10.1016/j.bbabio.2012.02.015
Alternate JournalBiochim. Biophys. Acta
PubMed ID22386882
Grant List / / Medical Research Council / United Kingdom
Research group: