title: Folding studies of Cox17 reveal an important interplay of cysteine oxidation and copper binding.
abstract: Cox17 is a key mitochondrial copper chaperone involved in the assembly of cytochrome c oxidase (COX). The NMR solution structure of the oxidized apoCox17 isoform consists of a coiled-coil conformation stabilized by two disulfide bonds involving Cys(26)/Cys(57) and Cys(36)/Cys(47). This appears to be a conserved tertiary fold of a class of proteins, localized within the mitochondrial intermembrane space, that contain a twin Cys-x(9)-Cys sequence motif. An isomerization of one disulfide bond from Cys(26)/Cys(57) to Cys(24)/Cys(57) is required prior to Cu(I) binding to form the Cu(1)Cox17 complex. Upon further oxidation of the apo-protein, a form with three disulfide bonds is obtained. The reduction of all disulfide bonds provides a molten globule form that can convert to an additional conformer capable of binding up to four Cu(I) ions in a polycopper cluster. This form of the protein is oligomeric. These properties are framed within a complete model of mitochondrial import and COX assembly.
authors.affiliation: Magnetic Resonance Center CERM and Department of Chemistry, University of Florence, Via Luigi Sacconi 6, Sesto Fiorentino, Florence 50019, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Arnesano
authors.forename: Erica
authors.initials: E
authors.lastname: Balatri
authors.forename: Lucia
authors.initials: L
authors.lastname: Banci
authors.forename: Ivano
authors.initials: I
authors.lastname: Bertini
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Winge
mesh_terms: D000595:Amino Acid Sequence; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D000079922:Copper Transport Proteins; D003545:Cysteine / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017510:Protein Folding; D021381:Protein Transport; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C100359:COX17 protein, S cerevisiae; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D003300:Copper; D003545:Cysteine