Molecular Mechanism of Hsp70 Chaperones: Interactions with Cochaperones and Substrates

This lecture delves into the molecular mechanism of Hsp70 chaperones, focusing on their interactions with cochaperones and substrates. Topics covered include the structure and mode of action of Hsp70, allosteric regulation, probing the kinetics of ATP-induced conformational changes, and the influence of cochaperones like GrpE and DnaJ on the dynamics of DnaK. The lecture also explores the conformational equilibria in both nucleotide states, the impact of substrates on DnaK-ATP dynamics, and the unfolding of protein clients by Hsp70-Hdj1. Additionally, it discusses the regulation of the heat shock response by HSF1, including the chaperone titration model and the thermosensing properties of HSF1.