Structures of the N-terminal and middle domains of E-coli Hsp90 and conformation changes upon ADP binding
Structures of the N-terminal and middle domains of E-coli Hsp90 and conformation changes upon ADP binding
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DOI：
10.1016/j.str.2004.12.018
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发表时间：
2005-04-01
期刊：
影响因子：
5.7
通讯作者：
Ke, HM
中科院分区：
文献类型：
--
作者：
Huai, Q;Wang, HC;Ke, HM
HSP90是一种丰富的分子伴侣，参与多种生物系统。我们报道了含有HtpG的N-末端和中间结构域的未连接和ADP结合片段的晶体结构。这些域并不像模型中经常描述的那样通过灵活的链接器连接，而是彼此紧密关联。单个HtpG结构域具有与DNA旋转酶B相似的折叠，但组装方式不同，这表明ATPase超家族的机制有所不同。ADP与N-末端结构域和中间结构域共同形成的大片段的子袋结合，并诱导N-末端结构域的构象变化。我们推测，这个大口袋可能是客户蛋白/辅伴侣蛋白的结合部位。模拟表明，ATP不暴露在分子表面，这意味着ATP对HSP90伴侣活性的激活是通过构象变化完成的。
Hsp90 is an abundant molecular chaperone involved in many biological systems. We report here the crystal structures of the unliganded and ADP bound fragments containing the N-terminal and middle domains of HtpG, an E. coli Hsp90. These domains are not connected through a flexible linker, as often portrayed in models, but are intimately associated with one another. The individual HtpG domains have similar folding to those of DNA gyrase B but assemble differently, suggesting somewhat different mechanisms for the ATPase superfamily. ADP binds to a subpocket of a large site that is jointly formed by the N-terminal and middle domains and induces conformational changes of the N-terminal domain. We speculate that this large pocket serves as a putative site for binding of client proteins/cochaperones. Modeling shows that ATP is not exposed to the molecular surface, thus implying that ATP activation of hsp90 chaperone activities is accomplished via conformational changes.