恢复者-SNX17组装和内体组分的结构基础
Amika Singla1, Daniel J Boesch2, Ho Yee Joyce Fung3
1Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.
Nature communications
|November 25, 2024
概括
排序Nexin 17 (SNX17) 将货物连接到回收复合体进行内体循环. 货物绑定释放SNX17的释放
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 排序Nexin 17 (SNX17) 对于内体循环至关重要,它通过与Retriever复合体相互作用来调解载荷蛋白质的运输.
- 控制SNX17-Retriever相互作用的精确分子机制尚未完全阐明.
研究的目的:
- 阐明Sorting Nexin 17 (SNX17) -Retriever复杂相互作用的结构和生化机制.
- 了解货物结合如何调节SNX17与Retriever的相互作用以及随后的内体体贩运.
主要方法:
- 生物化学测定 生物化学测定
- 低温电子显微镜 (cryo-EM) 是一种电子显微镜.
- 蛋白质组学是指蛋白质组学.
- 细胞成像 细胞成像
主要成果:
- SNX17存在于自抑制状态,其FERM域与其C端尾结合.
- 货物绑定到SNX17的FERM域释放C终端尾部,然后绑定到Retriever的VPS35L/VPS26C接口.
- 这种接口的破坏会损害货物回收,并改变血膜蛋白质组合.
- 猎犬的结合口袋容纳了具有酸性C端纹理的其他配体.
结论:
- 揭示了SNX17介导的内体载荷循环的新机制,涉及载荷诱导的SNX17C端尾部释放以绑定Retriever.
- 这些发现提供了对SNX17-Retriever相互作用及其由货物调节的结构性见解.
- 这项研究突出了Retriever与多种连接体相互作用的潜力,影响细胞贩运和潜在的病原体相互作用.
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