Structure of bacterial respiratory complex I

• Published in: Biochimica et biophysica acta Vol. 1857; no. 7; pp. 892 - 901
• Main Authors: Berrisford, John M., Baradaran, Rozbeh, Sazanov, Leonid A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2016
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - ultrastructure; Complex I; Electron transfer; Electron Transport; Electron Transport Complex I - chemistry; Electron Transport Complex I - ultrastructure; Membrane protein; Models, Chemical; Molecular Dynamics Simulation; Protein Conformation; Proton Pumps - chemistry; Proton Pumps - ultrastructure; Proton translocation; Respiratory chain; Structure-Activity Relationship; X-ray crystallography; X-ray crystallography; Electron transfer; Proton translocation; Respiratory chain; Membrane protein; Complex I
• ISSN: 0005-2728; 0006-3002; 1879-2650
• DOI: 10.1016/j.bbabio.2016.01.012

Complex I (NADH:ubiquinone oxidoreductase) plays a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation. It is the largest protein assembly of respiratory chains and one of the most elaborate redox membrane proteins known. Bacterial enzyme is about half the size of mitochondrial and thus provides its important “minimal” model. Dysfunction of mitochondrial complex I is implicated in many human neurodegenerative diseases. The L-shaped complex consists of a hydrophilic arm, where electron transfer occurs, and a membrane arm, where proton translocation takes place. We have solved the crystal structures of the hydrophilic domain of complex I from Thermus thermophilus, the membrane domain from Escherichia coli and recently of the intact, entire complex I from T. thermophilus (536kDa, 16 subunits, 9 iron–sulphur clusters, 64 transmembrane helices). The 95Å long electron transfer pathway through the enzyme proceeds from the primary electron acceptor flavin mononucleotide through seven conserved Fe–S clusters to the unusual elongated quinone-binding site at the interface with the membrane domain. Four putative proton translocation channels are found in the membrane domain, all linked by the central flexible axis containing charged residues. The redox energy of electron transfer is coupled to proton translocation by the as yet undefined mechanism proposed to involve long-range conformational changes. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt. [Display omitted] •Function and general architecture/organization of respiratory complex I is described.•Structure of bacterial complex I, representing the “core” of the enzyme, is described.•Unusual binding sites for substrates, NADH and quinone, are discussed.•Electron transfer pathway and proton translocation channels are discussed in detail.•Putative mechanism of coupling between electron transfer and proton translocation is discussed.