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Title | Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly and membrane cleavage. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 30, Issue 1, Page 81-90, Year 2023 |
Publish date | Jan 5, 2023 |
Authors | Kimi Azad / Delphine Guilligay / Cecile Boscheron / Sourav Maity / Nicola De Franceschi / Guidenn Sulbaran / Gregory Effantin / Haiyan Wang / Jean-Philippe Kleman / Patricia Bassereau / Guy Schoehn / Wouter H Roos / Ambroise Desfosses / Winfried Weissenhorn / |
PubMed 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 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. |
External links | Nat Struct Mol Biol / PubMed:36604498 |
Methods | EM (helical sym.) |
Resolution | 3.3 - 3.6 Å |
Structure data | EMDB-14630: Membrane-bound CHMP2A-CHMP3 filament (430 Angstrom diameter) EMDB-14631: Membrane-bound CHMP2A-CHMP3 filament (410 Angstrom diameter) |
Source |
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Keywords | CYTOSOLIC PROTEIN / Cryo Electron Microscopy / Helical Reconstruction / Membrane-bound CHMP2A-CHMP3 filament / Negative-curvature membrane |