The ESCRT complexes drive membrane scission in HIV-1 release, autophagosome closure, multivesicular body biogenesis, cytokinesis, and other cell processes. ESCRT-I is the most upstream complex and bridges the system to HIV-1 Gag in virus release. The crystal structure of the headpiece of human ESCRT-I comprising TSG101-VPS28-VPS37B-MVB12A was determined, revealing an ESCRT-I helical assembly with a 12-molecule repeat. Electron microscopy confirmed that ESCRT-I subcomplexes form helical filaments in solution. Mutation of VPS28 helical interface residues blocks filament formation in vitro and autophagosome closure and HIV-1 release in human cells. Coarse-grained (CG) simulations of ESCRT assembly at HIV-1 budding sites suggest that formation of a 12-membered ring of ESCRT-I molecules is a geometry-dependent checkpoint during late stages of Gag assembly and HIV-1 budding and templates ESCRT-III assembly for membrane scission. These data show that ESCRT-I is not merely a bridging adaptor; it has an essential scaffolding and mechanical role in its own right.

中文翻译：

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人ESCRT-1支架的螺旋组装逆拓扑膜分裂。

ESCRT复合物在HIV-1释放，自噬体封闭，多囊体生物发生，胞质分裂和其他细胞过程中驱动膜分裂。ESCRT-1是最上游的复合体，可将系统与病毒释放中的HIV-1 Gag桥接。确定了包含TSG101-VPS28-VPS37B-MVB12A的人ESCRT-1头戴式耳机的晶体结构，揭示了具有12个分子重复的ESCRT-1螺旋组件。电子显微镜证实，ESCRT-1亚复合物在溶液中形成螺旋丝。VPS28螺旋界面残基的突变可在体外阻止细丝形成，并在人类细胞中自噬体封闭和HIV-1释放。在HIV-1出芽位点进行ESCRT装配的粗粒（CG）模拟表明，在Gag装配以及HIV-1出芽和模板ESCRT的后期，形成12成员环的ESCRT-1分子是几何依赖的检查点-III组件用于膜断裂。这些数据表明，ESCRT-I不仅是桥接衔接子；而且 它本身具有重要的脚手架和机械作用。