Disease relevance of SCO1

• A search of the Bacillus subtilis genome identifies a potential homolog, ypmQ, of the inner mitochondrial membrane protein Sco1 from yeast [1].

High impact information on SCO1

• Cox17 is a 69-residue cysteine-rich, copper-binding protein that has been implicated in the delivery of copper to the Cu(A) and Cu(B) centers of cytochrome c oxidase via the copper-binding proteins Sco1 and Cox11, respectively [2].
• A number of conserved, positively charged residues may interact with complementary surfaces on Sco1 and Cox11, facilitating docking and copper transfer [2].
• Purified Sco1p sediments identical to Sco1p in crude extracts of mitochondria from wild type yeast or from a strain transformed with SCO1 on a high copy plasmid [3].
• The copper is not removed by the treatment of Sco1p with EDTA, indicating that it is bound with high affinity [3].
• 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 [4].

Chemical compound and disease context of SCO1

• The Bacillus subtilis genome contains a homologue of yeast Sco1, YpmQ (hereafter termed BSco), deletion of which leads to a phenotype lacking in caa3 (CuA-containing) oxidase activity but expressing normal levels of aa3 (quinol) oxidase activity [5].

Biological context of SCO1

• In contrast, neither copper, COX17 on a multicopy plasmid, or a combination of the two is able to restore respiration in sco1 mutants [6].
• Rescue of cox17 mutants by Sco1p suggests that this mitochondrial protein plays a role either in mitochondrial copper transport or insertion of copper into the active site of cytochrome oxidase [6].
• The complete sequence of a 33 kb fragment on the right arm of chromosome II from Saccharomyces cerevisiae reveals 16 open reading frames, including ten new open reading frames, five previously identified genes and a homologue of the SCO1 gene [7].
• Biogenesis of functional cytochrome c oxidase in yeast requires the product of the nuclear gene SCO1 [8].
• We report that the major transcription start sites of the yeast PET gene SCO1 are located at positions -149 and -125 relative to the AUG initiation codon of the SCO1 reading frame [9].

Anatomical context of SCO1

• SCO2 is a homologue of SCO1, whose product is also localized in the mitochondrial membrane but is not required for respiration [6].
• The observation that membrane localization of SCO1 is affected in mitochondria of a rho0 strain, hints at the possible involvement of mitochondrially coded components in ensuring proper membrane insertion [10].
• Sco1, a protein required for the proper assembly of cytochrome c oxidase, has a soluble domain anchored to the cytoplasmic membrane through a single transmembrane segment [11].

Associations of SCO1 with chemical compounds

• Based on the results obtained by isopycnic sucrose gradient centrifugation and by digitonin treatment of mitochondria, SCO1 is a component of the inner mitochondrial membrane [10].

Physical interactions of SCO1

• Here we show by affinity chromatography and coimmunoprecipitation that Sco1p interacts with subunit Cox2p [12].

Other interactions of SCO1

• The Saccharomyces cerevisiae gene SCO1 has been shown to play an essential role in the transfer of copper to the Cu(A)-centre of the mitochondrial cytochrome c oxidase subunit Cox2p [13].
• SCO1 was earlier reported to code for a mitochondrial inner membrane protein with an essential function in cytochrome oxidase assembly (Buchwald, P., Krummeck, G., and Rodel, G. (1991) Mol. Gen. Genet. 229, 413-420) [6].
• AUG codons in the RNA leader sequences of the yeast PET genes CBS1 and SCO1 have no influence on translation efficiency [9].
• These amino acids, which are conserved among the members of the Sco1p family, have been suggested to act in the reduction of the cysteines in the copper binding center of Cox2p and are discussed as ligands for copper [12].
• Its fold places Sco1 in a distinct subgroup of the functionally unrelated thioredoxin proteins [11].
• Using two in vivo assays that permit monitoring of the transient Sco1-Cox2 interaction, the mutant Sco1 molecules appear compromised in a function with Cox2 [14].

Analytical, diagnostic and therapeutic context of SCO1

• Data obtained from size-exclusion chromatography experiments with mitochondrial lysates suggest that full-length Sco1 may be oligomeric in vivo [4].

References