Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, T6G 2H7, Canada.
Department of Biotechnology and Biophysics, University of Würzburg, Würzburg, 97074, Germany.
Nat Commun. 2019 Mar 20;10(1):1273. doi: 10.1038/s41467-019-09299-3.
Hsp90 is a dimeric molecular chaperone that is essential for the folding and activation of hundreds of client proteins. Co-chaperone proteins regulate the ATP-driven Hsp90 client activation cycle. Aha-type co-chaperones are the most potent stimulators of the Hsp90 ATPase activity but the relationship between ATPase regulation and in vivo activity is poorly understood. We report here that the most strongly conserved region of Aha-type co-chaperones, the N terminal NxNNWHW motif, modulates the apparent affinity of Hsp90 for nucleotide substrates. The ability of yeast Aha-type co-chaperones to act in vivo is ablated when the N terminal NxNNWHW motif is removed. This work suggests that nucleotide exchange during the Hsp90 functional cycle may be more important than rate of catalysis.
Hsp90 是一种二聚体分子伴侣，对于数百种客户蛋白的折叠和激活是必不可少的。共伴侣蛋白调节 ATP 驱动的 Hsp90 客户激活循环。Aha 型共伴侣是 Hsp90 ATP 酶活性的最强刺激物，但 ATP 酶调节与体内活性之间的关系知之甚少。我们在这里报告，Aha 型共伴侣中最保守的区域，即 N 端 NxNNWHW 基序，调节 Hsp90 对核苷酸底物的表观亲和力。当去除酵母 Aha 型共伴侣的 N 端 NxNNWHW 基序时，其在体内发挥作用的能力被消除。这项工作表明，Hsp90 功能循环期间的核苷酸交换可能比催化速率更为重要。
