Hsp70 Molecular Chaperones: Conformational Flexibility and Function

This lecture explores the conformational and functional flexibility of Hsp70 molecular chaperones, focusing on folding intermediates, native and unfolded states, intramolecular contacts, oligomers, and the Hsp70 functional cycle. It delves into the architecture, domain organization, and the impact of AMPylation and substitutions on the conformational landscape. The instructor discusses the thermodynamics and kinetics of the Hsp70 cycle, the control of ATP binding, and the fine-tuning of the Hsp70 conformational ensemble. Additionally, the lecture covers the role of Ca²+ in altering the BiP cycle, perturbations in the substrate-binding domain, and the dynamic 'hot spots' controlling the BIP cycle.