Alternative ATPase domain interactions in eukaryotic Hsp70 chaperones

Hsp70 molecular chaperones are essential components for maintaining protein homeostasis within cells. They interact with substrate or client proteins in a well characterised fashion that is regulated by ATP and supported by co-chaperones. In eukaryotes there is a vast array of Hsp70 isoforms that may facilitate adaption to a particular cellular compartment and distinct biological role. Emerging data indicate a novel type of interaction between Hsp70 and client protein that does not fit with the classical Hsp70 ATP regulated substrate mechanism. In this review, we highlight Hsp70 ATPase domain interactions with binding partners from various biological systems that we refer to as Hsp70 ATPase alternative binding proteins or HAAB proteins. We identify common mechanistic features that may define how Hsp70 operates when associating with proteins in this alternative HAAB mode of action.

Automated summary

Hsp70 molecular chaperones are vital for maintaining protein homeostasis. They interact with client proteins in a regulated manner, supported by ATP and co-chaperones. Recent findings suggest a novel type of interaction between Hsp70 and client proteins, termed Hsp70 ATPase alternative binding proteins or HAAB proteins. Common mechanistic features of Hsp70 in this alternative mode of action are identified.