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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Cattle
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Chromatography
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Copper / chemistry
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Crystallography, X-Ray
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Cysteine / chemistry
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Disulfides / chemistry
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Electron Transport Complex IV / chemistry*
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Genotype
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Humans
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Hydrogen Peroxide / chemistry
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Hydrogen Peroxide / pharmacology
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Ligands
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Membrane Proteins / chemistry*
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Mitochondria / metabolism*
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Mitochondrial Proteins / chemistry
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Models, Molecular
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Molecular Chaperones / chemistry
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Molecular Sequence Data
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Mutation
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Mutation, Missense
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Oxidation-Reduction
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Peroxidases / chemistry
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Peroxides / chemistry
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Point Mutation
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Protein Conformation
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Protein Structure, Tertiary
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Sequence Homology, Amino Acid
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Thioredoxins / chemistry
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Time Factors
Substances
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Disulfides
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Ligands
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Membrane Proteins
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Mitochondrial Proteins
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Molecular Chaperones
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Peroxides
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SCO1 protein, human
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Thioredoxins
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Copper
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Hydrogen Peroxide
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Peroxidases
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Electron Transport Complex IV
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Cysteine