Disease relevance of ATP5O

• This ATP5O subunit is a key structural component of the stalk of the mitochondrial respiratory chain F1F0-ATP synthase and as such may contribute in a gene dosage-dependent manner to the phenotype of Down syndrome (trisomy 21) [1].
• We propose that bovine mitochondrial OSCP is a functional analogue of subunit b in the Escherichia coli H+-ATPase [2].
• Immunological cross-reactivity was demonstrated between bovine, human, rat, Saccharomyces cerevisiae, Paracoccus denitrificans, and Escherichia coli for subunit 6; between bovine, human, and rat for subunits b, d, OSCP, and F6; and between bovine and rat for the DCCD binding proteolipid [3].

High impact information on ATP5O

• Recombinant OSCP was found to accumulate in the cytoplasmic inclusion bodies, by virtue of which the recombinant protein could be purified to greater than 85% purity by simple low speed centrifugation of cell lysates [4].
• A full-length cDNA clone encoding OSCP was isolated from a bovine heart cDNA library, and the mature form of OSCP was expressed in Escherichia coli using plasmid expression vector pKP1500 [4].
• Results showed that per mol of F1 there are in bovine heart mitochondria 1 mol each of d, OSCP, and IF1, and 2 mol each of b and F6 [5].
• The data clearly establish that OSCP is not a necessary component of the F0 proton channel nor is its presence required for conductance blockage by the inhibitors oligomycin or dicyclohexylcarbodiimide [6].
• In order to investigate the requirement of OSCP for passive proton conductance through mitochondrial F0, OSCP-depleted membrane preparations were obtained by extracting purified F1-F0 complexes with 4.0 M urea [6].

Chemical compound and disease context of ATP5O

• F0I-PVP and OSCP added to UPEc, promoted inhibition by N,N'-dicyclohexylcarbodiimide of passive H+ conduction and increased its binding affinity to subunit c of E. coli F0 [7].
• In the NH2-terminal sequence of the first 18 amino acids (NKELDPVQKLFVDKIREY), six identities with the NH2-terminal sequence of the oligomycin-sensitivity conferring protein (OSCP) are apparent, as well as less striking similarities with the OSCP related subunit delta of E. coli F1 [8].

Biological context of ATP5O

• These experiments indicate that the bovine and human inhibitor and bovine F6 proteins are encoded by single genes but suggest the possibility of the presence in both species of more than one gene (or pseudogenes) for the OSCP [9].
• The reassociated complex of Type II ATPase and 26,500-dalton ATPase binding protein or of oligomycin sensitivity conferral protein and Type II ATPase has properties similar to that of Type I ATPase [10].
• These results show that F1 (and/or OSCP) protects Fo thiols from diamide and are substantiated by the finding that the oligomycin sensitivity of ATP hydrolysis activity of isolated Complex V was also unaltered by diamide [11].
• Dimerization of oligomycin sensitivity conferral protein by oxidation with copper phenanthroline chelate abolishes its ability to interact with the Type II ATPase [10].
• The fluorescence probe 2'-O-(trinitrophenyl)adenosine-5'-triphosphate was bound to the nucleotide binding sites of the enzyme, whereas the probe 7-diethylamino-3'-(4'-maleimidylphenyl)-4-methylcoumarin was attached to the single sulfhydryl residue of isolated oligomycin sensitivity-conferring protein (OSCP), which was then reconstituted with F1 [12].

Anatomical context of ATP5O

• ATP synthase from bovine mitochondria: sequences of imported precursors of oligomycin sensitivity conferral protein, factor 6, and adenosinetriphosphatase inhibitor protein [9].
• Subunit interaction in the mitochondrial H+-translocating ATPase. The role of oligomycin sensitivity conferral protein and coupling factor 6 in ATPase binding and Pi-ATP exchange in mitochondrial membranes [13].
• Data on nested deletion mutations starting from the carboxyl terminus in OSCP demonstrated that, in each instance, the mutant form was expressed and the protein product was sequestered in cytoplasmic inclusion bodies, similar to the wild-type form [4].
• The binding parameters of [14C]OSCP with respect to the F0 sector of submitochondrial particles largely depleted of F1 and OSCP (AUA particles) have been explored [14].
• Addition of the purified mitochondrial FoI-PVP and oligomycin sensitivity-conferring (OSCP) proteins to the F1 stripped chromatophores restored the sensitivity of proton permeability to DCCD detected in untreated chromatophores [15].

Associations of ATP5O with chemical compounds

• The polypeptide patterns produced by cyanogen bromide cleavage indicates a similar but nonidentical pattern to the 26,500-dalton ATPase binding protein and the oligomycin sensitivity conferral protein [10].
• F1-ATPase and Type II ATPase require F6 in addition to oligomycin sensitivity conferral protein and FB to reconstitute 32Pi-ATP exchange activity in silicotungstic acid particles [13].
• These UF0 complexes had no intrinsic ATPase activity and were able to bind nearly the same amount of F1-ATPase in the presence of either OSCP or NH4+ ions alone, or a combination of the two [6].
• It was shown by S-carboxymethylation of cysteine residues with iodo-[2-14C]acetic acid that bovine F1F0-ATPase and the reconstituted F1.stalk complex, F1.OSCP.b'.d.F6, each contained one copy per complex of subunits b (or b'), OSCP and d, and that the separate stalk complex contained the same three subunits in the approximate molar ratio 1:1:1 [16].
• A molecular weight (Mr) of 22 000 for OSCP was determined by sodium dodecyl sulfate gel electrophoresis at different concentrations of the polyacrylamide gel [17].

Analytical, diagnostic and therapeutic context of ATP5O

• Studies to establish the structure/function relationships of oligomycin sensitivity-conferring protein (OSCP) of mitochondrial ATP synthase were carried out using genetic engineering and biochemical approaches [4].
• The residual complexes, referred to as UF0, were found to be deficient with respect to OSCP, as well as alpha, beta, and gamma subunits of F1-ATPase, but had a full complement of coupling factor 6 as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting techniques [6].
• The additional 26.5 kDa (delta) subunit is shown by immunoblotting and N-terminal amino acid sequencing to be similar to bovine oligomycin-sensitivity-conferring protein (OSCP) [18].
• From the circular dichroism spectrum of OSCP, 43% alpha-helical structure was calculated; the dichroism spectra of OSCP in H2O and D2O were identical [17].
• The monoclonal antibody 2B1B1 used in this study could bind as well to purified or membrane bound OSCP as shown previously by Protein A-gold immunocytochemistry and by competitive immunotitration [19].

References