Meyer Philippe, Prodromou Chrisostomos, Hu Bin, Vaughan Cara, Roe S Mark, Panaretou Barry, Piper Peter W, Pearl Laurence H
Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, SW3 6JB, London, United Kingdom.
Mol Cell. 2003 Mar;11(3):647-58. doi: 10.1016/s1097-2765(03)00065-0.
Activation of client proteins by the Hsp90 molecular chaperone is dependent on binding and hydrolysis of ATP, which drives a molecular clamp via transient dimerization of the N-terminal domains. The crystal structure of the middle segment of yeast Hsp90 reveals considerable evolutionary divergence from the equivalent regions of other GHKL protein family members such as MutL and GyrB, including an additional domain of new fold. Using the known structure of the N-terminal nucleotide binding domain, a model for the Hsp90 dimer has been constructed. From this structure, residues implicated in the ATPase-coupled conformational cycle and in interactions with client proteins and the activating cochaperone Aha1 have been identified, and their roles functionally characterized in vitro and in vivo.
热休克蛋白90（Hsp90）分子伴侣对客户蛋白的激活依赖于ATP的结合与水解，这通过N端结构域的瞬时二聚化驱动分子钳。酵母Hsp90中间片段的晶体结构显示，其与其他GHKL蛋白家族成员（如MutL和GyrB）的等效区域存在显著的进化差异，包括一个新折叠的额外结构域。利用N端核苷酸结合结构域的已知结构，构建了Hsp90二聚体模型。从该结构中，已鉴定出参与ATP酶偶联构象循环以及与客户蛋白和激活共伴侣Aha1相互作用的残基，并在体外和体内对其功能作用进行了表征。
