|Title||Structure of the membrane domain of respiratory complex I.|
|Publication Type||Journal Article|
|Year of Publication||2011|
|Authors||Efremov, RG, Sazanov, LA|
|Date Published||2011 Aug 07|
|Keywords||Antiporters, 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|
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.
|Grant List||MC_U105674180 / / Medical Research Council / United Kingdom|