在Golgi维护中的VCP-VCPIP1-p47三元复合体的结构基础
Binita Shah1,2, Moritz Hunkeler1,2, Ariana Bratt1,2
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nature communications
|August 28, 2025
概括
含有瓦洛辛的蛋白质 (VCP) 与p47和VCPIP1一起在细胞分裂后重建戈尔吉细胞. 结构研究揭示了这些蛋白质是如何形成一个复杂的,突出VCPID
科学领域:
- 细胞生物学
- 结构生物学
- 生物化学
背景情况:
- 含有瓦洛辛的蛋白质 (VCP/p97) 对于细胞过程至关重要,包括神经分裂后的戈尔吉重组.
- 已知的辅助因子是VCPIP1 (一个双酸酶) 和p47 (一种适配蛋白),它们有助于VCP在戈尔吉生物发生过程中.
研究的目的:
- 阐明VCP-VCPIP1和VCP-VCPIP1-p47三元复合体的结构组织.
- 了解这些辅助因子与VCP相互作用以促进戈尔吉重组的分子机制.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定VCP- VCPIP1和VCP- VCPIP1- p47复合物的结构.
- 进行生物化学测定和细胞实验以验证结构发现和评估功能意义.
主要成果:
- VCPIP1通过两个不同的接口连接VCP:VCP N域/VCPIP1 UBX域和VCP D2域/VCPIP1 VCPID区域.
- p47 UBX 域与 VCP N 域相竞争,但不会干扰 VCPID 相互作用.
- VCPIP1的VCPID区域对于增强VCP的二化酶活性和确保适当的戈尔吉组合至关重要.
结论:
- 这项研究提供了关键VCP辅助因子复合物的高分辨率结构,揭示了新的相互作用接口.
- VCPID被确定为VCP介导的Golgi重组和DUB活动增强的关键功能元素.
- 这些发现提供了关于VCP及其监管伙伴在细胞过程中的复杂相互作用的重要见解.
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