小热冲击蛋白质客户端封存和诱导多分散性的机制
Adam P Miller1,2, Steve L Reichow1,2
1Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland OR 97239, U.S.A.
bioRxiv : the preprint server for biology
|December 16, 2024
概括
小热冲击蛋白 (sHSPs) 通过与受损蛋白结合来保护细胞免受压力. 新的冷EM结构揭示了这些陪伴者 (sHSPs) 如何组装和捕获客户端蛋白质,维持细胞蛋白质稳定.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 细胞生物学 细胞生物学
背景情况:
- 小热冲击蛋白 (sHSPs) 是关键的伴侣,在细胞应激期间防止蛋白质聚合.
- 它们在维持蛋白质稳定中的作用至关重要,功能障碍与人类疾病有关.
- 由于它们的动态性质和客户诱导的变化性,理解sHSP机制具有挑战性.
研究的目的:
- 阐明sHSP客户端封存的分子机制.
- 调查sHSP可塑性和组装的结构基础.
- 提供关于在压力下陪伴者与客户互动的见解.
主要方法:
- 高分辨率的冷电子显微镜 (cryo-EM).
- 对 *Methanocaldococcus jannaschii* sHSP (mjHSP16.5) 的apo和客户端结合状态的结构分析.
- 调查sHSP寡合化和客户互动动态.
主要成果:
- 在apo和客户端绑定状态下确定mjHSP16.5的冷EM结构.
- 揭示了sHSPs如何识别,结合和隔离不稳定的客户端蛋白质.
- 证明了客户端诱导的稳定性两极分化和sHSPs的更高阶组装.
- 确定了多个组装路径和子单元插入机制.
结论:
- sHSPs利用动态结构重组来隔离各种客户端蛋白质.
- 客户参与触发了合作组合,增强了封存能力.
- 在sHSP复合体中的多分散性是它们应激反应功能的组成部分.
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