Structural basis of CHMP2A–CHMP3 ESCRT-III polymer assembly and membrane cleavage - Groupe Entrée et bourgeonnement des virus à enveloppe / Entry and Budding of Enveloped Viruses Group (EBEV) Access content directly
Journal Articles Nature Structural and Molecular Biology Year : 2023

Structural basis of CHMP2A–CHMP3 ESCRT-III polymer assembly and membrane cleavage

Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly and membrane cleavage.

Kimi Azad
Gregory Effantin
Guy Schoehn
Wouter Roos
Winfried Weissenhorn

Abstract

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.
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Dates and versions

hal-03962316 , version 1 (01-02-2023)

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Kimi Azad, Delphine Guilligay, Cecile Boscheron, Sourav Maity, Nicola de Franceschi, et al.. Structural basis of CHMP2A–CHMP3 ESCRT-III polymer assembly and membrane cleavage. Nature Structural and Molecular Biology, 2023, 30 (1), pp.81-90. ⟨10.1038/s41594-022-00867-8⟩. ⟨hal-03962316⟩
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