title: Characterization of COX17, a yeast gene involved in copper metabolism and assembly of cytochrome oxidase.
abstract: Mutations in the COX17 gene of Saccharomyces cerevisiae cause a respiratory deficiency due to a block in the production of a functional cytochrome oxidase complex. Because cox17 mutants are able to express both the mitochondrially and nuclearly encoded subunits of cytochrome oxidase, the Cox17p most likely affects some late posttranslational step of the assembly pathway. A fragment of yeast nuclear DNA capable of complementing the mutation has been cloned by transformation of the cox17 mutant with a library of genomic DNA. Subcloning and sequencing of the COX17 gene revealed that it codes for a cysteine-rich protein with a molecular weight of 8,057. Unlike other previously described accessory factors involved in cytochrome oxidase assembly, all of which are components of mitochondria, Cox17p is a cytoplasmic protein. The cytoplasmic location of Cox17p suggested that it might have a function in delivery of a prosthetic group to the holoenzyme. A requirement of Cox17p in providing the copper prosthetic group of cytochrome oxidase is supported by the finding that a cox17 null mutant is rescued by the addition of copper to the growth medium. Evidence is presented indicating that Cox17p is not involved in general copper metabolism in yeast but rather has a more specific function in the delivery of copper to mitochondria.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Glerum
authors.forename: A
authors.initials: A
authors.lastname: Shtanko
authors.forename: A
authors.initials: A
authors.lastname: Tzagoloff
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D027682:Cation Transport Proteins; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D000079922:Copper Transport Proteins; D003576:Electron Transport Complex IV / Q000096:biosynthesis*; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D005800:Genes, Fungal; D005838:Genotype; D008928:Mitochondria / Q000378:metabolism; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D010641:Phenotype; D014176:Protein Biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins
chemical_list: C100359:COX17 protein, S cerevisiae; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D005656:Fungal Proteins; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D003300:Copper; D003576:Electron Transport Complex IV