How the ESCRT-III-like protein Vipp1 assembles polymeric super-structures to mitigate membrane stress
Award Number
BB/W008181/1Status / Stage
ActiveDates
1 July 2022 -30 June 2026
Duration (calculated)
03 years 11 monthsFunder(s)
BBSRC (UKRI)Funding Amount
£698,586.00Funder/Grant study page
BBSRC UKRIContracted Centre
Imperial College LondonPrincipal Investigator
Dr Harry LowPI Contact
h.low@imperial.ac.ukPI ORCID
0000-0002-1226-3217WHO Catergories
Understanding Underlying DiseaseDisease Type
Dementia (Unspecified)CPEC Review Info
| Reference ID | 698 |
|---|---|
| Researcher | Reside Team |
| Published | 07/07/2023 |
Data
| Award Number | BB/W008181/1 |
|---|---|
| Status / Stage | Active |
| Start Date | 20220701 |
| End Date | 20260630 |
| Duration (calculated) | 03 years 11 months |
| Funder/Grant study page | BBSRC UKRI |
| Contracted Centre | Imperial College London |
| Funding Amount | £698,586.00 |
Abstract
Membrane remodelling and repair are essential for all cells. Systems that undertake these functions include Vipp1/IM30 in photosynthetic plastids, PspA in bacteria, and ESCRT-III in eukaryotes. In an exciting discovery, we recently showed that Vipp1, PspA and ESCRT-III form an ancient membrane remodelling superfamily with broad function, from membrane repair in bacteria, cell division in archaea to endosome biogenesis in humans. Understanding how these proteins work has broad implication for cyanobacteria/plant biology and biotechnology, and human pathologies such as viral infection, antimicrobial resistance (AMR), and neurodegeneration. Here we aim to understand the mechanism that underlies Vipp1 membrane remodelling in cyanobacteria. We aim to provide a molecular context for how Vipp1 stabilises membranes, mitigates membrane stress and promotes thylakoid biogenesis. ESCRT-III systems are complex with multiple components often forming composite filaments. Vipp1 represents the exciting potential of a readily tractable model by which to dissect the conserved and underlying mechanistic principles for how ESCRT-III-like proteins sculpt and exert force on the membrane. We have three aims that utilise electron and light microscopy, biophysics and biochemistry: 1) to understand how Vipp1 builds polymeric superstructures such as helical and planar filaments, and how Vipp1 morphs between them. The comparison of these superstructures will give insight into how ESCRT-III-like proteins flex, bind and deform membrane. 2) to describe the dynamics of Vipp1-mediated membrane remodelling. A simplified cell-like system will be reconstituted in vitro with Vipp1 mixed with Vipp1 binding proteins and membrane, and the effects quantitatively measured. 3) to investigate how Vipp1 is regulated by finding novel VBPs in Nostoc punctiforme. We aim to test the hypothesis that Vipp1 may form composite filaments and co-complex with NTPases to modulate assembly dynamics.
Aims
We aim to provide a molecular context for how Vipp1 stabilises membranes, mitigates membrane stress and promotes thylakoid biogenesis.