Structure of the hydrophilic domain of respiratory complex I from Thermus thermophilus.

TitleStructure of the hydrophilic domain of respiratory complex I from Thermus thermophilus.
Publication TypeJournal Article
Year of Publication2006
AuthorsSazanov, LA, Hinchliffe, P
JournalScience
Volume311
Issue5766
Pagination1430-6
Date Published2006 Mar 10
ISSN1095-9203
KeywordsAnimals, Bacterial Proteins, Binding Sites, Crystallography, X-Ray, Electron Transport Complex I, Iron-Binding Proteins, Oxidation-Reduction, Protein Conformation, Protein Folding, Protein Structure, Tertiary, Protein Subunits, Thermus thermophilus
Abstract

Respiratory complex I plays a central role in cellular energy production in bacteria and mitochondria. Its dysfunction is implicated in many human neurodegenerative diseases, as well as in aging. The crystal structure of the hydrophilic domain (peripheral arm) of complex I from Thermus thermophilus has been solved at 3.3 angstrom resolution. This subcomplex consists of eight subunits and contains all the redox centers of the enzyme, including nine iron-sulfur clusters. The primary electron acceptor, flavin-mononucleotide, is within electron transfer distance of cluster N3, leading to the main redox pathway, and of the distal cluster N1a, a possible antioxidant. The structure reveals new aspects of the mechanism and evolution of the enzyme. The terminal cluster N2 is coordinated, uniquely, by two consecutive cysteines. The novel subunit Nqo15 has a similar fold to the mitochondrial iron chaperone frataxin, and it may be involved in iron-sulfur cluster regeneration in the complex.

DOI10.1126/science.1123809
Alternate JournalScience
Citation Key10.1126/science.1123809
PubMed ID16469879
Grant ListMC_U105674180 / / Medical Research Council / United Kingdom