FIGURE 1: Hch1 interaction to yeast Hsp90 and phosphorylation of Y627 in human Hsp90 impact client chaperoning through restricting Hsp90 conformational changes. (A) Normal ATP-driven client chaperoning in both humans and yeast. Appropriate interaction of Hsp90 with Hch1 (yeast) or phosphorylation of Hsp90-Y627 (human) promotes release of chaperoned client. (B) Deregulated Hch1 interaction with yeast Hsp90 restricts its conformational flexibility, resulting in reduced client chaperoning. (C) Deregulated phosphorylation of human Hsp90 at Y627 phenocopies consequences of deregulated Hch1 interaction in yeast.