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.
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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-pp.ucl.ac.uk/id/eprint/10109894 |
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