The endosomal sorting complex required for transport (ESCRT) is a multi-protein complex, which facilitates many processes in biological cells. In particular, it is central to trafficking of membrane proteins and budding of certain enveloped viruses such as HIV. Recent experimental data show that certain ESCRT proteins that associate with lipid membranes assemble into polymer-like structures. These protein aggregates, or polymers, act to buckle the membrane locally and, in this way, drive the formation of vesicles. However, the mechanism how they do that remains very much unclear. The objective of our project is to explore theoretical models, which could shed light on this important and complicated process. To start the project, we are going to combine continuum and molecular models for lipid membranes and calculate the energy required for membrane budding and vesicle formation. The later energy should be next compared with the energy of binding of the ESCRT proteins to the lipid membranes. The binding energy can be estimated from the detailed structure analysis of ESCRT components. Comparison of the two energy scales should rule out some of the possible mechanisms of vesicle formation driven by ESCRT. In next stages of the project we want to study the energetically possible processes of vesicle formation by simulating the ESCRT components that act to deform the lipid membranes. Since the ESCRT protein aggregates are of a mesoscopic size, their activity and interactions with the membranes will require multi-scale analysis and leave room form methods development. As the ESCRT still is not a well-studied complex, and a lot of new experimental data on its structure and functions are coming out currently, we believe that the outcome of our project will substantially contribute to the understanding of this 'molecular machinery'.
Field of science
- /medical and health sciences/health sciences/infectious disease/RNA virus
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins
Call for proposal
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