Hydrophilic Domain of Respiratory ComplexIfromThermus thermophilus

Abstract

AbstractComplex 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 complex of bacterial and mitochondrial respiratory chains. Mitochondrial complex I is a major source of reactive oxygen species (ROS), which may be one of the causes of aging. Dysfunction of the enzyme is implicated in many human neurodegenerative diseases. Complex I is an L‐shaped multisubunit protein assembly consisting of a hydrophilic peripheral arm and a hydrophobic membrane arm. The crystal structure of the hydrophilic domain of complex I fromThermus thermophiluswas solved recently. This subcomplex consists of eight subunits and contains all the redox centers of the enzyme, including nine iron–sulfur clusters. The electron transfer pathway through the enzyme is about 95 Å long, proceeding from the primary electron acceptor flavin mononucleotide through seven conserved iron–sulfur clusters to the quinone‐binding site at the interface with the membrane domain. The structure of the complete enzyme and the coupling mechanism are not yet known.