Harker-Kirschneck, Lena;
(2022)
Physical mechanisms of ESCRT-III-driven membrane deformations.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The endosomal sorting complex required for transport (ESCRT) is an ancient piece of protein machinery that has been highly conserved throughout evolution and across species, from archaea to eukaryotes. Its main sub-complex ESCRT-III forms spiral- and helical-shaped filaments with the unique ability to deform and cut membranes from the inside of the membrane neck. These filaments are involved in a wide range of membrane deformation and cutting processes, such as endosomal vesicle budding, viral budding, membrane healing and cytokinesis. Despite many attempts, a comprehensive mechanism that would encompass all of the observed modes of membrane deformation is still missing. Here we developed a minimal coarse-grained model of ESCRT-III filaments that can capture the experimentally reported cases of ESCRT-III driven membrane remodelling, including both downward and upward buckles, membrane tubules, cones, buds and archaeal cell division. Archaeal cells, despite their structural simplicity, share machinery and evolutionary origins with eukaryotes and some of them — like eukaryotes — require ESCRT-III proteins for division. All ESCRT filaments in our model are defined by their intrinsic curvature (Rtarget) and the angle in which their membrane attraction site faces (tilt angle τ). If the attraction site faces downwards (τ = 0°), the filament will assemble in the shape of a spiral and flatten the membrane, whereas for larger tilts, it will form a conical and finally tubular shape and cause deformations in the membrane. We propose that ESCRT filaments have the ability to modify Rtarget and τ, either by forming copolymers with other ESCRT agents, or via the depolymerising unit Vps4, that has the ability to replace or remove ESCRT isoforms from the copolymer. The composition of a copolymer determines the ultimate curvature and tilt of the final filament, and the stepwise modification of the filament’s composition leads to changes in its resulting ability to deform and cut membranes.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Physical mechanisms of ESCRT-III-driven membrane deformations |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10161544 |
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