The conserved NxNNWHW motif in Aha-type co-chaperones modulates the kinetics of Hsp90 ATPase stimulation
The conserved NxNNWHW motif in Aha-type co-chaperones modulates the kinetics of Hsp90 ATPase stimulation
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DOI：
10.1038/s41467-019-09299-3
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发表时间：
2019-03-20
影响因子：
16.6
通讯作者：
LaPointe, Paul
中科院分区：
文献类型：
--
作者：
Mercier, Rebecca;Wolmarans, Annemarie;LaPointe, Paul
Hsp90是一种二聚体分子伴侣，对数百种客户蛋白的折叠和激活至关重要。协同伴侣蛋白调节atp驱动的Hsp90客户端激活周期。aha型共伴侣是Hsp90 atp酶活性最有效的刺激物，但atp酶调节与体内活性之间的关系尚不清楚。我们在这里报道了aha型共伴侣蛋白中最保守的区域，N端NxNNWHW基序，调节Hsp90对核苷酸底物的表观亲和力。当去除N端NxNNWHW基序时，酵母ah型共伴侣蛋白在体内的作用能力被削弱。这项工作表明，在Hsp90功能周期中核苷酸交换可能比催化速率更重要。
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.