title: Structure of the membrane domain of respiratory complex I.
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.
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Rouslan G
authors.initials: RG
authors.lastname: Efremov
authors.forename: Leonid A
authors.initials: LA
authors.lastname: Sazanov
mesh_terms: D017920:Antiporters / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D018360:Crystallography, X-Ray; D042967:Electron Transport Complex I / Q000737:chemistry* / Q000378:metabolism*; D004926:Escherichia coli / Q000737:chemistry*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D017136:Ion Transport; D008239:Lysine / Q000378:metabolism; D008958:Models, Molecular; D009243:NAD / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011522:Protons; D014451:Ubiquinone / Q000378:metabolism
chemical_list: D017920:Antiporters; D029968:Escherichia coli Proteins; C098483:NADH dehydrogenase subunit 4; D021122:Protein Subunits; D011522:Protons; D009243:NAD; D014451:Ubiquinone; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; D008239:Lysine