人类ERAD逆转移复合体的冷-EM结构
Bing Rao1, Qian Wang2, Deqiang Yao2,3
1Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Science advances
|October 13, 2023
概括
细胞内膜网关联降解 (ERAD) 使用Derlin-1和p97将错误折叠的蛋白质移出ER. 这项研究揭示了它们的复杂结构,以及p97如何
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 细胞内膜网关联降解 (ERAD) 对于维持蛋白质平衡至关重要.
- ERAD将错误折叠的蛋白质从内分泌网膜 (ER) 光层获取到细胞质中进行降解.
- 通过ER膜逆转移的机制尚未完全理解.
研究的目的:
- 阐明ERAD逆转移机制的结构基础.
- 了解Derlin-1和p97在蛋白质降解中的功能相互作用.
- 为了揭示基质进入ER膜通道的机制.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定德林-1-p97复合物的结构.
- 对异构-十元复合结构的分析.
- 研究由ATP水解引起的形状变化.
主要成果:
- 冷-EM结构显示了Derlin-1四分体和p97六分体的不对称复合物.
- 在Derlin-1和p97组件中观察到协调的挤压运动.
- 由ATP水解驱动的p97的形状变化,将Derlin-1通道打开成"U"形,促进基质进入.
- 确定了p97和Derlin-1之间的功能复合体,将ERAD逆转移与ATP水解联系起来.
结论:
- 该研究揭示了Derlin-1通道打开的结构机制,允许基质逆转移.
- 这些发现表明p97的ATP依赖活性与ERAD通路的合.
- 这项工作为细胞内的蛋白质质量控制和降解途径提供了关键的见解.
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