Hsp90-p23-GR的结构揭示了Hsp90客户端重塑机制
Chari M Noddings1, Ray Yu-Ruei Wang1, Jill L Johnson2
1Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Nature
|December 23, 2021
概括
热冲击蛋白90 (Hsp90) 和它的协伴蛋白p23将葡萄糖皮质体受体 (GR) 重塑为原生,连接体的状态. 这显示Hsp90
科学领域:
- 分子生物学
- 结构生物学
- 生物化学
背景情况:
- 热冲击蛋白90 (Hsp90) 是许多客户蛋白的折叠和激活所必需的关键分子伴侣.
- 葡萄皮质受体 (GR) 是一个关键的客户蛋白质,其活性严重依赖Hsp90.
- 之前的研究表明,Hsp70抑制GR连接物结合,而Hsp90和p23则恢复这种结合,但其分子机制尚不清楚.
研究的目的:
- 阐明GR客户端蛋白质的Hsp90介导重塑的分子机制.
- 呈现人类GR-Hsp90-p23成熟复合物的冷电子显微镜 (cryo-EM) 结构.
- 了解HSP90及其辅助器p23如何决定特定客户的折叠结果.
主要方法:
- 用冷电子显微镜 (cryo-EM) 确定人类GR-Hsp90-p23复合物的结构.
- 结构分析以揭示Hsp90复合体内的GR结构.
- 生物化学测试以评估p23在稳定GR和增强连接中的作用.
主要成果:
- 低温-EM结构显示了在Hsp90光体内的折叠的,与连接体结合的GR连接体域.
- 通过C-终端螺旋,协伴蛋白p23直接稳定原生GR,从而改善了连接物结合.
- 这种结构与之前观察到的未折叠的客户端-Hsp90复合体形成鲜明对比,突出显示了客户端特定的折叠控制.
结论:
- 通过与客户直接互动,HSP90可以决定客户特定的折叠结果.
- 这项研究为任何Hsp90客户提供了第一个完整的护理周期,详细介绍了GR重塑的分子机制.
- 这项工作提供了对Hsp90机制对客户蛋白的动态调节的关键见解.
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