Structure of bacterial respiratory complex I Journal Article


Author(s): Berrisford, John M; Baradaran, Rozbeh ; Sazanov, Leonid A
Article Title: Structure of bacterial respiratory complex I
Affiliation IST Austria
Abstract: 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 (536. kDa, 16 subunits, 9 iron-sulphur clusters, 64 transmembrane helices). The 95. Å 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.
Keywords: membrane protein; Complex I; Respiratory chain; X-ray crystallography; Electron transfer; Proton translocation
Journal Title: Biochimica et Biophysica Acta - Bioenergetics
Volume: 1857
Issue 7
ISSN: 0005-2728
Publisher: Elsevier  
Date Published: 2016-06-01
Start Page: 892
End Page: 901
Sponsor: funded by the Medical Research Council (Grant number MC_U105674180)
DOI: 10.1016/j.bbabio.2016.01.012
Open access: no