Structural analysis of E-coli hsp90 reveals dramatic nucleotide-dependent conformational rearrangements
Structural analysis of E-coli hsp90 reveals dramatic nucleotide-dependent conformational rearrangements
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DOI：
10.1016/j.cell.2006.09.027
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发表时间：
2006-10-20
期刊：
影响因子：
64.5
通讯作者：
Agard, David A.
中科院分区：
文献类型：
--
作者：
Shiau, Andrew K.;Harris, Seth F.;Agard, David A.
在真核生物中，90千道尔顿热休克蛋白（hsp 90）伴侣蛋白家族的普遍存在和丰富的成员促进细胞信号传导，增殖和生存中重要的蛋白质的广泛阵列的折叠和构象变化。在这里，我们描述了核苷酸对全长HtpG，大肠杆菌hsp 90 ortho-log的结构的影响。通过电子显微镜，核苷酸自由，AMPPNP绑定，ADP绑定状态的HtpG采取完全不同的构象。通过X射线晶体学将无核苷酸和ADP结合的HtpG的结构表征扩展到更高的分辨率。在不存在核苷酸的情况下，HtpG表现出“开放”构象，其中每个单体的三个结构域将疏水元件存在于由二聚体形成的大裂缝中。相比之下，AIDP结合驱动剧烈的构象变化，使这些疏水元件会聚并相互屏蔽溶剂，这表明核苷酸可以控制客户蛋白结合和释放的机制。
In eukaryotes, the ubiquitous and abundant members of the 90 kilodalton heat-shock protein (hsp90) chaperone family facilitate the folding and conformational changes of a broad array of proteins important in cell signaling, proliferation, and survival. Here we describe the effects of nucleotides on the structure of full-length HtpG, the Escherichia coli hsp90 ortho-log. By electron microscopy, the nucleotide-free, AMPPNP bound, and ADP bound states of HtpG adopt completely distinct conformations. Structural characterization of nucleotide-free and ADP bound HtpG was extended to higher resolution by X-ray crystallography. In the absence of nucleotide, HtpG exhibits an "open" conformation in which the three domains of each monomer present hydrophobic elements into the large cleft formed by the dimer. By contrast, AIDP binding drives dramatic conformational changes that allow these hydrophobic elements to converge and shield each other from solvent, suggesting a mechanism by which nucleotides could control client protein binding and release.