ESCRT公司
劈理(地质)
膜
生物物理学
化学
细胞生物学
生物
小泡
生物化学
断裂(地质)
古生物学
作者
Kimi Azad,Delphine Guilligay,Cécile Boscheron,Sourav Maity,Nicola De Franceschi,Guidenn Sulbarán,Grégory Effantin,Haiyan Wang,Jean-Philippe Kleman,Patricia Bassereau,Guy Schoehn,Wouter H. Roos,Ambroise Desfosses,Winfríed Weissenhorn
标识
DOI:10.1038/s41594-022-00867-8
摘要
The endosomal sorting complex required for transport (ESCRT) is a highly conserved protein machinery that drives a divers set of physiological and pathological membrane remodeling processes. However, the structural basis of ESCRT-III polymers stabilizing, constricting and cleaving negatively curved membranes is yet unknown. Here we present cryo-EM structures of membrane-coated CHMP2A–CHMP3 filaments from Homo sapiens of two different diameters at 3.3 and 3.6 Å resolution. The structures reveal helical filaments assembled by CHMP2A–CHMP3 heterodimers in the open ESCRT-III conformation, which generates a partially positive charged membrane interaction surface, positions short N-terminal motifs for membrane interaction and the C-terminal VPS4 target sequence toward the tube interior. Inter-filament interactions are electrostatic, which may facilitate filament sliding upon VPS4-mediated polymer remodeling. Fluorescence microscopy as well as high-speed atomic force microscopy imaging corroborate that VPS4 can constrict and cleave CHMP2A–CHMP3 membrane tubes. We therefore conclude that CHMP2A–CHMP3–VPS4 act as a minimal membrane fission machinery. The cryo-EM structures of ESCRT-III CHMP2A and CHMP3 filaments reveal their mode of polymerization and interaction with negatively curved membrane. VPS4 constricts and cleaves the ESCRT-III CHMP2A–CHMP3 membrane tubes, thus acting as a minimal membrane fission machinery.
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