title: Middle domain of human Hsp90 isoforms differentially binds Aha1 in human cells and alters Hsp90 activity in yeast.
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.
authors.affiliation: Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego St., Warsaw 02-106, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Synoradzki
authors.affiliation: Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego St., Warsaw 02-106, Poland. Electronic address: bieganowski@imdik.pan.pl.
authors.forename: Pawel
authors.initials: P
authors.lastname: Bieganowski
mesh_terms: D057809:HEK293 Cells; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C515652:AHSA1 protein, human; C117748:HCH1 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D051034:Inhibitor of Apoptosis Proteins; D018832:Molecular Chaperones; D020033:Protein Isoforms; D029701:Saccharomyces cerevisiae Proteins
keywords: Aha1; Hsp90; Human; Isoform; Yeast; cIAP1