title: Cytochrome c oxidase: structure, function, and membrane topology of the polypeptide subunits.
abstract: Mitochondrial cytochrome c oxidase and its bacterial homologs catalyze electron transfer and proton translocation reactions across membranes. The eukaryotic enzyme complex consists of a large number of polypeptide subunits. Three of the subunits (I, II, and III) are mitochondrially encoded while the remaining 6 (yeast) to 10 (bovine) are nuclear encoded. Antibody and chemical-labelling experiments suggest that subunits I-III and most (but not all) of the nuclear-encoded subunits span the inner mitochondrial membrane. Subunits I and II are the catalytic core of the enzyme. Subunit I contains haem a, haem a3 and CuB, while subunit II contains CuA and the cytochrome c binding site. Subunit III and most of the nuclear subunits are essential for the assembly of a functional catalytic enzyme. Some nuclear subunits are present as isozymes, although little functional difference has yet been detected between enzyme complexes composed of different isozymes. Therefore, any additional role attributed to the nuclear-encoded subunits beyond that of enzyme assembly must be tentative. We suggest that enough evidence exists to support the idea that modification of the larger nuclear subunits (IV, V, and possibly VI) can effect enzyme turnover in vitro. Whether this is a physiological control mechanism remains to be seen.
authors.affiliation: Division of Biomolecular Sciences, King's College London, U.K.
authors.forename: C E
authors.initials: CE
authors.lastname: Cooper
authors.forename: P
authors.initials: P
authors.lastname: Nicholls
authors.forename: J A
authors.initials: JA
authors.lastname: Freedman
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001665:Binding Sites; D002462:Cell Membrane / Q000201:enzymology*; D003574:Cytochrome c Group / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D007425:Intracellular Membranes / Q000201:enzymology; D007527:Isoenzymes; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D015003:Yeasts / Q000201:enzymology
chemical_list: D000906:Antibodies; D003574:Cytochrome c Group; D007527:Isoenzymes; D003576:Electron Transport Complex IV