title: The copper chaperone for superoxide dismutase.
abstract: Copper is distributed to distinct localizations in the cell through diverse pathways. We demonstrate here that the delivery of copper to copper/zinc superoxide dismutase (SOD1) is mediated through a soluble factor identified as Saccharomyces cerevisiae LYS7 and human CCS (copper chaperone for SOD). This factor is specific for SOD1 and does not deliver copper to proteins in the mitochondria, nucleus, or secretory pathway. Yeast cells containing a lys7Delta null mutation have normal levels of SOD1 protein, but fail to incorporate copper into SOD1, which is therefore devoid of superoxide scavenging activity. LYS7 and CCS specifically restore the biosynthesis of holoSOD1 in vivo. Elucidation of the CCS copper delivery pathway may permit development of novel therapeutic approaches to human diseases that involve SOD1, including amyotrophic lateral sclerosis.
authors.affiliation: Division of Toxicological Sciences, Department of Environmental Health Sciences, Johns Hopkins University School of Public Health, Baltimore, Maryland 21205, USA. vculotta@phnet.sph.jhu.edu
authors.forename: V C
authors.initials: VC
authors.lastname: Culotta
authors.forename: L W
authors.initials: LW
authors.lastname: Klomp
authors.forename: J
authors.initials: J
authors.lastname: Strain
authors.forename: R L
authors.initials: RL
authors.lastname: Casareno
authors.forename: B
authors.initials: B
authors.lastname: Krems
authors.forename: J D
authors.initials: JD
authors.lastname: Gitlin
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D003300:Copper / Q000378:metabolism*; D000079922:Copper Transport Proteins; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism*
chemical_list: C100359:COX17 protein, S cerevisiae; C491006:COX17 protein, human; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D005656:Fungal Proteins; D018832:Molecular Chaperones; D011506:Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D003300:Copper; C095735:LYS7 protein, S cerevisiae; D013482:Superoxide Dismutase