Substrate binding drives large-scale conformational changes in the Hsp90 molecular chaperone.
Substrate binding drives large-scale conformational changes in the Hsp90 molecular chaperone.
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DOI：
10.1016/j.molcel.2011.01.029
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发表时间：
2011-04-08
期刊：
影响因子：
16
通讯作者：
Agard DA
中科院分区：
文献类型：
--
作者：
Street TO;Lavery LA;Agard DA
热休克蛋白90是一种普遍存在的分子伴侣。以前的结构分析表明，热休克蛋白90可以采用大量的结构不同的构象，然而，这种灵活性的功能作用还不清楚。在这里，我们研究了底物结合的结构后果与一个模型系统，其中热休克蛋白90与部分折叠的蛋白质（Δ131Δ），葡萄球菌核酸酶的一个充分研究的片段相互作用。SAXS测量结果显示，在apo条件下，Hsp 90在Δ131Δ周围部分闭合，并且在AMPPNP存在下，Δ131Δ以增加的亲和力结合到Hsp 90的完全闭合状态。FRET测量表明Δ131Δ加速核苷酸驱动的开放/闭合转变，并刺激Hsp 90水解ATP。NMR测量显示，Hsp 90结合到Δ131Δ的特定的高度结构化区域。这些结果表明，热休克蛋白90优先结合局部结构区域在全球展开的蛋白质，这种结合驱动功能的变化，通过降低限速构象障碍的伴侣。
Hsp90 is a ubiquitous molecular chaperone. Previous structural analysis demonstrated that Hsp90 can adopt a large number of structurally distinct conformations; however, the functional role of this flexibility is not understood. Here we investigate the structural consequences of substrate binding with a model system in which Hsp90 interacts with a partially folded protein (Δ131Δ), a well-studied fragment of staphylococcal nuclease. SAXS measurements reveal that under apo conditions, Hsp90 partially closes aroundΔ131Δ, and in the presence of AMPPNP,Δ131Δbinds with increased affinity to Hsp90's fully closed state. FRET measurements show thatΔ131Δaccelerates the nucleotide-driven open/closed transition and stimulates ATP hydrolysis by Hsp90. NMR measurements reveal that Hsp90 binds to a specific, highly structured region ofΔ131Δ. These results suggest that Hsp90 preferentially binds a locally structured region in a globally unfolded protein, and this binding drives functional changes in the chaperone by lowering a rate-limiting conformational barrier.
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DOI：
10.1073/pnas.132393699
发表时间：
2002-08-20
影响因子：
11.1
作者：
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影响因子：
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作者：
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影响因子：
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DOI：
10.1016/j.bbrc.2010.08.047
发表时间：
2010-09-17
影响因子：
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作者：
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通讯作者：
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