Structure, Function and Regulation of the Hsp90 Machinery

TLDR: The recent progress made in understanding the Hsp90 machinery is discussed, which influences the conformational cycle, co-chaperone interaction, and inter-domain communications.

Abstract: Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations ATP binding triggers directionality in these conformational changes and leads to a more compact state To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation They influence the conformational cycle, co-chaperone interaction, and inter-domain communications In this review, we discuss the recent progress made in understanding the Hsp90 machinery