Heat-shock protein 90: intrinsic peptidase activity and in vitro long-term self-processing.
When tested on Suc-Leu-Leu-Val-Tyr-MCA as substrate, purified full-length hsp90 displays a low "chymotrypsin-like" peptidase activity which is activated by Ca++ and Mg++ ions. On the other hand, using long-term in vitro experiments, we demonstrate the ability of hsp90 to convert into a 73 kDa truncated product. This autocatalytic degradation proceeds from the C-terminal end of the full-length hsp90 and shifts the oligomers toward monomeric truncated forms. This corresponds to an intermolecular process as addition of exogenous 73 kDa product speeds up the maturation kinetics. The peptidase activity is enhanced in the 73 kDa product and is sensitive to peptide aldehyde inhibitors but only partially to lactone compounds. The degradation process itself presents a great degree of similarity with the peptidase activity toward either the inhibitors or the tested ions. Neither 20S proteasome nor m-calpain are responsible for the observed activities. Indeed, the self-processing is a consequence of the peptidase activity which appears to be an intrinsic property of the chaperone. The functional importance of these findings is discussed.