ATPase Activity and ATP-dependent Conformational Change in the Co-chaperone HSP70/HSP90-organizing Protein (HOP)

Co-chaperones help to maintain cellular homeostasis by modulating the activities of molecular chaperones involved in protein quality control. The HSP70/HSP90-organizing protein (HOP) is a co-chaperone that cooperates with HSP70 and HSP90 in catalysis of protein folding and maturation in the cytosol. We show here that HOP has ATP-binding activity comparable to that of HSP70/HSP90, and that HOP slowly hydrolyzes ATP. Analysis of deletion mutants revealed that the ATPase domain of HOP is in the N-terminal TPR1-DP1-TPR2A segment. In addition, HOP changes its conformation in the presence of ATP. These results indicate that HOP is a unique co-chaperone that undergoes an ATP-dependent conformational change. Background: HOP assists protein transfer in the HSP70- and HSP90-dependent protein-folding pathway. Results: HOP hydrolyzed ATP, and the region containing amino acids 1–359 (TPR1-TPR2A) was required for hydrolysis and direct interaction with ATP. Conclusion: HOP has slow ATPase activity and changes its conformation upon ATP hydrolysis. Significance: This is the first demonstration of the ATPase activity of HOP, and may enhance our understanding of the physiological function.