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

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Azad, Kimi | Guilligay, Delphine | Boscheron, Cécile | Maity, Sourav | de Franceschi, Nicola | Sulbaran, Guidenn | Effantin, Grégory | Wang, Haiyang | Kleman, Jp | Bassereau, Patricia | Schoehn, Guy | Roos, Wouter, H | Desfosses, Ambroise | Weissenhorn, Winfried

Edité par CCSD ; Nature Publishing Group -

International audience. 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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