An Hsp70/Hsp90 Co-Chaperone That Functions Within and Beyond Hsp70/Hsp90 Protein Folding Pathways

Molecular chaperones and their co-chaperones are crucial for the facilitation of efficient protein folding, and prevention of denaturation and aggregation of nascent polypeptides. Hsp70/Hsp90 organizing protein (Hop), a co-chaperone of the two major molecular chaperones, heat shock protein 70 (Hsp70) and heat shock protein 90 (Hsp90), facilitates their interaction by acting as an adaptor between the two chaperones, so that substrate is efficiently transferred from Hsp70 to Hsp90. Although initial studies reported its scaffolding properties to be its primary function, recent findings suggest an additional modulatory effect of Hop on the activities of Hsp70 and Hsp90. In addition, a more diverse role of Hop, involving structurally and functionally unrelated biomolecules and complexes, is currently being revealed. This review focuses on the integratory and modulatory effects of Hop on the Hsp70 and Hsp90 protein folding pathways, and puts forward evidence and theories regarding its multifaceted roles within various biological systems.