Yeast Sco1, a protein essential for cytochrome c oxidase function is a Cu(I)-binding protein

• Published in: The Journal of biological chemistry Vol. 276; no. 45; pp. 42520 - 42526
• Main Authors: Nittis, T, George, G N, Winge, D R
• Format: Journal Article
• Language: English
• Published: United States 09.11.2001
• Subjects: Amino Acid Motifs; Carrier Proteins - chemistry; Copper - metabolism; copper-binding protein; Dimerization; Electron Transport Complex IV - physiology; Ligands; Membrane Proteins - chemistry; Membrane Proteins - physiology; Sco1 protein
• ISSN: 0021-9258
• DOI: 10.1074/jbc.M107077200

Sco1 is a conserved essential protein, which has been implicated in the delivery of copper to cytochrome c oxidase, the last enzyme of the electron transport chain. In this study, we show for the first time that the purified C-terminal domain of yeast Sco1 binds one Cu(I)/monomer. X-ray absorption spectroscopy suggests that the Cu(I) is ligated via three ligands, and we show that two cysteines, present in a conserved motif CXXXC, and a conserved histidine are involved in Cu(I) ligation. The mutation of any one of the conserved residues in Sco1 expressed in yeast abrogates the function of Sco1 resulting in a non-functional cytochrome c oxidase complex. Thus, the function of Sco1 correlates with Cu(I) binding. Data obtained from size-exclusion chromatography experiments with mitochondrial lysates suggest that full-length Sco1 may be oligomeric in vivo.