6VME

Human ESCRT-I heterotetramer headpiece

6VME の概要

• エントリーDOI: 10.2210/pdb6vme/pdb
• 分子名称: Tumor susceptibility gene 101 protein, Vacuolar protein sorting-associated protein 37B, Multivesicular body subunit 12A, ... (5 entities in total)
• 機能のキーワード: endosomal transport, hiv release, macroautophagy, protein transport
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 24
• 化学式量合計: 204222.14

構造登録者

Flower, T.G.,Hurley, J.H.,Tjahjono, N. (登録日: 2020-01-27, 公開日: 2020-05-20, 最終更新日: 2023-10-11)

主引用文献

Flower, T.G.,Takahashi, Y.,Hudait, A.,Rose, K.,Tjahjono, N.,Pak, A.J.,Yokom, A.L.,Liang, X.,Wang, H.G.,Bouamr, F.,Voth, G.A.,Hurley, J.H.
A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission.
Nat.Struct.Mol.Biol., 27:570-580, 2020

PubMed Abstract: 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.

PubMed: 32424346
DOI: 10.1038/s41594-020-0426-4

実験手法

X-RAY DIFFRACTION (2.19 Å)