Aha1 binds to Hsp90α with higher affinity than to Hsp90β.
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High affinity of Aha1 for Hsp90 is mediated by the M-domain of Hsp90α.
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C-terminal fragment of Hsp90α M-domain confers slow growth phenotype in yeast.
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Hsp90α is more depended than Hsp90β on co-chaperoning by Aha1.
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Effective chaperoning of cIAP1 depends on interaction with the N-domain of Hsp90β.
Abstract
Hsp90 is an essential chaperone for more than 200 client proteins in eukaryotic cells. The human genome encodes two highly similar cytosolic Hsp90 proteins called Hsp90α and Hsp90β. 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 Hsp90α. The distinction depends on the middle domain of Hsp90. The middle domain of Hsp90α 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 Hsp90α and Hsp90β may be responsible for the isoform-specific interactions with selected proteins. Also shown here within, we determine that preferential chaperoning of cIAP1 by Hsp90β is mediated by the N-terminal domain of this isoform.
