Conformational dynamics of free and membrane-bound human Hsp70 in model cytosolic and endo-lysosomal environments

Abstract

Calvaresi et al. use hydrogen-deuterium exchange coupled to mass spectrometry to compare the conformational dynamics of the human heat shock protein Hsp70 when free and when associated with liposomes composed of common lysosomal lipids. They also investigate the conformational changes occuring in Hsp70 when transitioning from the pH of the cytosol to that of early and late lysosomes. This study provides new molecular insights into how Hsp70 can stabilize endo-lysosomal membranes and inhibit the uncontrolled release of degradative enzymes linked to lysosomal storage disorders.