Middle domain of human Hsp90 isoforms differentially binds Aha1 in human cells and alters Hsp90 activity in yeast

摘要

Hsp90 is an essential chaperone for more than 200 client proteins in eulcaryotic cells. The human genome encodes two highly similar cytosolic Hsp90 proteins called Hsp90 alpha and Hsp90 beta. Most of the client proteins can interact with either Hsp90 protein; however, only a handful client proteins and one co-chaperone that interact specifically with one of the Hsp90 isoforms were identified. Structural differences underlying these isoform-specific interactions were not studied. Here we report for the first time that the Hsp90 co-chaperone Aha1 interacts preferentially with Hsp90 alpha. The distinction depends on the middle domain of Hsp90. The middle domain of Hsp90 alpha is also responsible for the slow growth phenotype of yeasts that express this isoform as a sole source of Hsp90. These results suggest that differences in the middle domain of Hsp90 alpha and Hsp90 beta may be responsible for the isoform-specific interactions with selected proteins. Also shown here within, we determine that preferential chaperoning of cIAP1 by Hsp90 beta is mediated by the N-terminal domain of this isoform. (C) 2014 Elsevier B.V. All rights reserved.