Past Event: Oden Institute Seminar

How Hsp70s move and pull part protein complexes and aggregates

Rui Sousa, UT Health Science Center, San Antonio

Abstract

In addition to their roles in protein folding, Hsp70 chaperones function as motors that pull proteins into the ER and mitochondria, and that dissociate protein complexes and aggregates. How these physical transformations are effected has been unclear, but recent theoretical and experimental work indicates that neither a classical Brownian ratchet (in which an Hsp70 asymmetrically captures spontaneous fluctuations in its substrates), nor a power-stroke mechanism (in which a conformational change exerts a directed force coincident with a step in the ATP hydrolysis cycle) explain Hsp70 action. Instead, Hsp70s exhibit an unprecedented mechano-chemical cycle in which co-chaperones load Hsp70s onto the flexible peptide segments of their substrates within structurally constrained spaces, allowing the Hsp70s to dynamically generate pushing and pulling forces against those substrates.