PDF(Pubmed)
Abstract：
Hsp90 is a molecular chaperone that acts on its clients through an ATP-dependent and conformationally dynamic functional cycle. The cochaperone Accelerator of Hsp90 ATPase, or Ahsa1, is the most potent stimulator of Hsp90 ATPase activity. Ahsa1 stimulates the rate of Hsp90 ATPase activity through a conserved motif, NxNNWHW. Metazoan Ahsa1, but not yeast, possesses an additional 20 amino acid peptide preceding the NxNNWHW motif that we have called the intrinsic chaperone domain (ICD). The ICD of Ahsa1 diminishes Hsp90 ATPase stimulation by interfering with the function of the NxNNWHW motif. Furthermore, the NxNNWHW modulates Hsp90\'s apparent affinity to Ahsa1 and ATP. Lastly, the ICD controls the regulated recruitment of Hsp90 in cells and its deletion results in the loss of interaction with Hsp90 and the glucocorticoid receptor. This work provides clues to how Ahsa1 conserved regions modulate Hsp90 kinetics and how they may be coupled to client folding status.
摘要：
Hsp90是一种分子伴侣，通过ATP依赖性和构象动态功能循环作用于其客户。Hsp90ATP酶的陪伴促进剂，或Ahsa1是Hsp90ATP酶活性的最有效刺激剂。Ahsa1通过保守的基序刺激Hsp90ATPase活性的速率，NxNNWHW.后生动物Ahsa1，但不是酵母，在NxNNWHW基序之前具有额外的20个氨基酸肽，我们将其称为内在伴侣结构域（ICD）。Ahsa1的ICD通过干扰NxNNWHW基序的功能来减少Hsp90ATP酶的刺激。此外，NxNNWHW调节Hsp90对Ahsa1和ATP的表观亲和力。最后,ICD控制Hsp90在细胞中的调节募集,其缺失导致与Hsp90和糖皮质激素受体相互作用的丧失.这项工作为Ahsa1保守区如何调节Hsp90动力学以及它们如何与客户端折叠状态耦合提供了线索。
