Structure of the membrane domain of respiratory complex I.

TitleStructure of the membrane domain of respiratory complex I.
Publication TypeJournal Article
Year of Publication2011
AuthorsEfremov, R. G., and Sazanov L. A.
JournalNature
Volume476
Issue7361
Pagination414-20
Date Published2011 Aug 25
ISSN1476-4687
KeywordsAntiporters, Cell Membrane, Crystallography, X-Ray, Electron Transport Complex I, Escherichia coli, Escherichia coli Proteins, Ion Transport, Lysine, Models, Molecular, NAD, NADH Dehydrogenase, Protein Binding, Protein Folding, Protein Structure, Tertiary, Protein Subunits, Protons, Ubiquinone
Abstract

Complex I is the first and largest enzyme of the respiratory chain, coupling electron transfer between NADH and ubiquinone to the translocation of four protons across the membrane. It has a central role in cellular energy production and has been implicated in many human neurodegenerative diseases. The L-shaped enzyme consists of hydrophilic and membrane domains. Previously, we determined the structure of the hydrophilic domain. Here we report the crystal structure of the Esherichia coli complex I membrane domain at 3.0 Å resolution. It includes six subunits, NuoL, NuoM, NuoN, NuoA, NuoJ and NuoK, with 55 transmembrane helices. The fold of the homologous antiporter-like subunits L, M and N is novel, with two inverted structural repeats of five transmembrane helices arranged, unusually, face-to-back. Each repeat includes a discontinuous transmembrane helix and forms half of a channel across the membrane. A network of conserved polar residues connects the two half-channels, completing the proton translocation pathway. Unexpectedly, lysines rather than carboxylate residues act as the main elements of the proton pump in these subunits. The fourth probable proton-translocation channel is at the interface of subunits N, K, J and A. The structure indicates that proton translocation in complex I, uniquely, involves coordinated conformational changes in six symmetrical structural elements.

DOI10.1038/nature10330
Alternate JournalNature
PubMed ID21822288
Grant List / / Medical Research Council / United Kingdom
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