Reactive cysteines of the 90-kDa heat shock protein, Hsp90.
The 90-kDa heat shock protein (Hsp90) is the most abundant molecular chaperone of the eukaryotic cytoplasm. Its cysteine groups participate in the interactions of Hsp90 with the heme-regulated eIF-2alpha kinase and molybdate, a stabilizer of Hsp90-protein complexes. In our present studies we investigated the reactivity of the sulfhydryl groups of Hsp90. Our data indicate that Hsp90 as well as two Hsp90 peptides containing Cys-521 and Cys-589/590 are able to reduce cytochrome c. The effect of Hsp90 can be blocked by sulfhydryl reagents including arsenite and cadmium, which indicates the involvement of the vicinal cysteines Cys589/590 in the reduction of cytochrome c. Hsp90 neither reduces the disulfide bonds of insulin nor possesses a NADPH:quinone oxidoreductase activity. Oxidizing conditions impair the chaperone activity of Hsp90 toward citrate synthase. The high and specific reactivity of Hsp90 cysteine groups toward cytochrome c may indicate a role of this chaperone in modulation of the redox status of the cytosol in resting and apoptotic cells.
Nardai
G
G
Department of Medical Chemistry, Semmelweis University, Budapest, Hungary.
Sass
B
B
Eber
J
J
Orosz
G
G
Csermely
P
P
D000595:Amino Acid Sequence; D000818:Animals; D003545:Cysteine / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000378:metabolism; D011490:Protein Disulfide Reductase (Glutathione) / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013439:Sulfhydryl Reagents / Q000378:metabolism
D003574:Cytochrome c Group; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D010446:Peptide Fragments; D013439:Sulfhydryl Reagents; D011490:Protein Disulfide Reductase (Glutathione); D003545:Cysteine