Chaperone Mechanism of Grp94: Elucidating ER Protein Quality Control

This lecture delves into the chaperone mechanism of Grp94, an essential ER resident molecular chaperone. It explores the role of ER Hsp90 and Hsp70 in protein homeostasis, client protein activation, and collaboration with cochaperones. The highly conserved Grp94 assists in stabilizing and reactivating client proteins, with ATP-dependent conformational changes. The interaction between Hsp90s and Hsp70s, the function of J-proteins in substrate interactions, and the stimulation of BIP ATP hydrolysis are also discussed. The lecture investigates the collaboration between Grp94 and the BiP chaperone system, the role of ATP binding/hydrolysis in protein refolding, and the importance of a fully functional BiP system in client remodeling. It concludes by examining the reverse mechanism of Grp94/BiP compared to cytosolic chaperones.