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Changes in ESCRT-III filament geometry drive membrane remodelling and fission in sillico

Lena Harker-Kirschneck, Buzz Baum, View ORCID ProfileAndela Šarić
doi: https://doi.org/10.1101/559898
Lena Harker-Kirschneck
1Department of Physics & Astronomy, University College London, London, United Kingdom
2Institute for the Physics of Living Systems, University College London, London, United Kingdom
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Buzz Baum
2Institute for the Physics of Living Systems, University College London, London, United Kingdom
3MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom
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Andela Šarić
1Department of Physics & Astronomy, University College London, London, United Kingdom
2Institute for the Physics of Living Systems, University College London, London, United Kingdom
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  • ORCID record for Andela Šarić
  • For correspondence: a.saric@ucl.ac.uk
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Abstract

ESCRT-III is a membrane remodelling filament with the unique ability to cut membranes from the inside of the membrane neck. It is essential for the final stage of cell division, the formation of vesicles, the release of viruses, and membrane repair. Distinct to other cytoskeletal filaments, ESCRT-III filaments do not consume energy, but work in conjunction with another ATP-consuming complex. Despite rapid progress in describing the cell biology of ESCRT-III, we lack an understanding of the physical mechanisms behind its force production and membrane remodelling. Here we present a minimal coarse-grained model that that captures all the experimentally reported cases of ESCRT-III driven membrane sculpting, including the formation of downward and up-ward cones and tubules. This model suggests that a change in the geometry of membrane bound ESCRT-III filaments induces transitions between a flat spiral and a 3D helix to drive membrane deformation. We then show that such repetitive filament geometry transitions can induce the fission of cargo-containing vesicles. The mechanistic principles revealed here will enable manipulation of ESCRT-III-driven processes in cells and in guiding the engineering of synthetic membrane-sculpting systems.

Footnotes

  • ↵* E-mail: b.baum{at}ucl.ac.uk, a.saric{at}ucl.ac.uk

  • - results for the ESCRT-III-driven membrane fission when the cargo pre-forms a deeep deformation have been added (Fig. 4b) - clarification of the role of Vps4 ATP-ase in our model -clarificaiton on how we suggest the transitions in the filament geometries are achieved - minor changes to terminology and wording throughout the text - main results have been repeated using an explicit membrane bilayer (SI)

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 10, 2019.
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Changes in ESCRT-III filament geometry drive membrane remodelling and fission in sillico
Lena Harker-Kirschneck, Buzz Baum, Andela Šarić
bioRxiv 559898; doi: https://doi.org/10.1101/559898
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Changes in ESCRT-III filament geometry drive membrane remodelling and fission in sillico
Lena Harker-Kirschneck, Buzz Baum, Andela Šarić
bioRxiv 559898; doi: https://doi.org/10.1101/559898

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