Crystal structure and activity of human p23, a heat shock protein 90 co-chaperone

p23 is a co-chaperone for the heat shock protein, hsp90. This protein binds hsp90 and participates in the folding of a number of cell regulatory prote ins, but its activities are still unclear. We have solved a crystal structu re of human p23 lacking 35 residues at the COOH terminus. The structure rev eals a disulfide-linked dimer with each subunit containing eight beta-stran ds in a compact antiparallel beta-sandwich fold, In solution, however, p23 is primarily monomeric and the dimer appears to be a minor component. Conse rved residues are clustered on one face of the monomer and define a putativ e surface region and binding pocket for interaction(s) with hsp90 or protei n substrates, p23 contains a COOH-terminal tail that is apparently less str uctured and is unresolved in the crystal structure, This tail is not needed for the binding of pas to hsp90 or to complexes with the progesterone rece ptor. However, the tail is necessary for optimum active chaperoning of the progesterone receptor, as well as the passive chaperoning activity of p23 i n assays measuring inhibition of heat-induced protein aggregation.