title: Crystal structure of human SCO1: implications for redox signaling by a mitochondrial cytochrome c oxidase "assembly" protein.
abstract: Human SCO1 and SCO2 are copper-binding proteins involved in the assembly of mitochondrial cytochrome c oxidase (COX). We have determined the crystal structure of the conserved, intermembrane space core portion of apo-hSCO1 to 2.8 A. It is similar to redox active proteins, including thioredoxins (Trx) and peroxiredoxins (Prx), with putative copper-binding ligands located at the same positions as the conserved catalytic residues in Trx and Prx. SCO1 does not have disulfide isomerization or peroxidase activity, but both hSCO1 and a sco1 null in yeast show extreme sensitivity to hydrogen peroxide. Of the six missense mutations in SCO1 and SCO2 associated with fatal mitochondrial disorders, one lies in a highly conserved exposed surface away from the copper-binding region, suggesting that this region is involved in protein-protein interactions. These data suggests that SCO functions not as a COX copper chaperone, but rather as a mitochondrial redox signaling molecule.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Williams
authors.forename: Carolyn
authors.initials: C
authors.lastname: Sue
authors.forename: Graham S
authors.initials: GS
authors.lastname: Banting
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: D Moira
authors.initials: DM
authors.lastname: Glerum
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Hendrickson
authors.forename: Eric A
authors.initials: EA
authors.lastname: Schon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002845:Chromatography; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D003576:Electron Transport Complex IV / Q000737:chemistry*; D005838:Genotype; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000737:chemistry; D010545:Peroxides / Q000737:chemistry; D017354:Point Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000737:chemistry; D013997:Time Factors
chemical_list: D004220:Disulfides; D008024:Ligands; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D010545:Peroxides; C489345:SCO1 protein, human; D013879:Thioredoxins; D003300:Copper; D006861:Hydrogen Peroxide; D010544:Peroxidases; D003576:Electron Transport Complex IV; D003545:Cysteine