An Hsp90 co-chaperone protein in yeast is functionally replaced by site-specific posttranslational modification in humans

作者：Zuehlke Abbey D; Reidy Michael; Lin Coney; LaPointe Paul; Alsomairy Sarah; Lee D Joshua; Rivera Marquez Genesis M; Beebe Kristin; Prince Thomas; Lee Sunmin; Trepel Jane B; Xu Wanping; Johnson Jill; Masison Daniel; Neckers Len^*

来源：Nature Communications, 2017, 8(1): 15328.

DOI：10.1038/ncomms15328

Heat shock protein 90 (Hsp90) is an essential eukaryotic molecular chaperone. To properly chaperone its clientele, Hsp90 proceeds through an ATP-dependent conformational cycle influenced by posttranslational modifications (PTMs) and assisted by a number of co-chaperone proteins. Although Hsp90 conformational changes in solution have been well-studied, regulation of these complex dynamics in cells remains unclear. Phosphorylation of human Hsp90a at the highly conserved tyrosine 627 has previously been reported to reduce client interaction and Aha1 binding. Here we report that these effects are due to a long-range conformational impact inhibiting Hsp90a N-domain dimerization and involving a region of the middle domain/carboxy-terminal domain interface previously suggested to be a substrate binding site. Although Y627 is not phosphorylated in yeast, we demonstrate that the non-conserved yeast co-chaperone, Hch1, similarly affects yeast Hsp90 (Hsp82) conformation and function, raising the possibility that appearance of this PTM in higher eukaryotes represents an evolutionary substitution for HCH1.

• 出版日期2017-5-24