转运必需内体分选复合物螺旋纤丝Vps24-Vps2的冷冻电镜结构研究
刘德生#，李耀旺#，孙 珊*
（1.膜生物学国家重点实验室，北京生物结构前沿研究中心，清华大学生命科学学院，北京 100084；2.南方科技大学生命科学学院，广东 深圳 518005）
摘 要 转运必需内体分选复合物-III（endosomal sorting complex required for transport-III，ESCRT-III）介导了一系列细胞膜重塑事件，包括多囊体的形成、细胞分裂和病毒释放等。这些过程的关键步骤之一是将ESCRT-III蛋白亚基组装成纤丝状结构。在本研究中，作者利用冷冻电镜技术解析了由Vps24和Vps2融合蛋白（Vps24-Vps2）形成的双链螺旋纤丝的结构，分辨率为4.07Å。在该结构中，呈伸展构象的Vps24-Vps2单体首先形成反向结合的二聚体，二聚体之间再错位结合形成一股螺旋，两股螺旋互相缠绕最终形成纤丝。该结构为理解ESCRT-III丝状结构组装以及解聚过程提供了结构基础。
关键词 转运必需内体分选复合物；ESCRT；Vps24；Vps2，冷冻电镜结构
中图分类号： Q7；Q71；Q244 文献标识码：ADoi:10.3969/j.issn.1000-6281.2025.01.004
Cryo-EM structure of the ESCRT-III Vps24-Vps2 filament
LIU Desheng#，LI Yao-wang#，SUN Shan*
(1. State Key Laboratory of Membrane Biology, Beijing Frontier Research Center for Biological Structures, School of Life Sciences, Tsinghua University, Beijing 100084；2. School of Life Sciences, Southern University of Science and Technology, Shenzhen Guangdong 518005, China)
Abstract The cellular ESCRT-III proteins mediate a variety of membrane remodeling activities events such as multivesicular body biogenesis, midbody abscission during cytokinesis, wound plasma membrane repair, and enveloped virus budding. The assembly of ESCRT-III subunits into filament-like structures is essential for these processes. In this study, we used cryo-electron microscopy to resolve the structure of a double-stranded helical filament formed by a chimeric ESCRT-III subunit Vps24-Vps2 from Saccharomyces cerevisiae at a resolution of 4.07 Å. In each protofilament, the Vps24-Vps2 monomer is in an extended open conformation and assemble in a misaligned manner. Neighboring Vps24-2 monomers between two protofilaments adopt an inverse arrangement to entangle each other into a filament. Our structure provides a structural basis for understanding the assembly and disassembly of ESCRT-III filaments.
Keywords endosomal sorting complex required for transport；Vps24；Vps2；Cryo-EM structure
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