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An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission

Pfitzner, A-K; Mercier, V; Jiang, X; Moser von Filseck, J; Baum, B; Šarić, A; Roux, A; (2020) An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission. Cell , 182 (5) 1140-1155.e18. 10.1016/j.cell.2020.07.021. Green open access

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Abstract

The endosomal sorting complex required for transport-III (ESCRT-III) catalyzes membrane fission from within membrane necks, a process that is essential for many cellular functions, from cell division to lysosome degradation and autophagy. How it breaks membranes, though, remains unknown. Here, we characterize a sequential polymerization of ESCRT-III subunits that, driven by a recruitment cascade and by continuous subunit-turnover powered by the ATPase Vps4, induces membrane deformation and fission. During this process, the exchange of Vps24 for Did2 induces a tilt in the polymer-membrane interface, which triggers transition from flat spiral polymers to helical filament to drive the formation of membrane protrusions, and ends with the formation of a highly constricted Did2-Ist1 co-polymer that we show is competent to promote fission when bound on the inside of membrane necks. Overall, our results suggest a mechanism of stepwise changes in ESCRT-III filament structure and mechanical properties via exchange of the filament subunits to catalyze ESCRT-III activity.

Type: Article
Title: An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2020.07.021
Publisher version: https://doi.org/10.1016/j.cell.2020.07.021
Language: English
Additional information: © 2020 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: CHMP1, CHMP4, Did2, ESCRT, ESCRT-III, Ist1, Snf7, Vps2, in vitro reconstitution, membrane fission, membrane remodeling
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy
URI: https://discovery.ucl.ac.uk/id/eprint/10109894
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