Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly and membrane cleavage - Archive ouverte HAL
Article Dans Une Revue Nature Structural and Molecular Biology Année : 2023

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

Kimi Azad
  • Fonction : Auteur
Delphine Guilligay
  • Fonction : Auteur
Cécile Boscheron
  • Fonction : Auteur
  • PersonId : 988207
Sourav Maity
  • Fonction : Auteur
Nicola de Franceschi
Guidenn Sulbaran
  • Fonction : Auteur
Grégory Effantin
Haiyang Wang
  • Fonction : Auteur
Jp Kleman
Guy Schoehn
Wouter H Roos
  • Fonction : Auteur
Ambroise Desfosses
Winfried Weissenhorn

Résumé

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 electron microscopy structures of membrane-coated CHMP2A-CHMP3 filaments 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 towards 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 CHMP2A-CHMP3 polymers and VPS4 can constrict and cleave narrow membrane tubes, thus acting as a minimal membrane fission machinery.
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Dates et versions

hal-03869486 , version 1 (24-11-2022)

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Kimi Azad, Delphine Guilligay, Cécile 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, pp.81-90. ⟨10.1038/s41594-022-00867-8⟩. ⟨hal-03869486⟩
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