Proteins from the Endosomal Sorting Complexes Required for Transport ESCRT)-III remodel lipid membranes in cells of all three Domains of life, yet the molecular mechanism has so far only been speculated on. A minimal subset of three ESCRT-III proteins that can reshape membranes into helical tubes in vitro. Using cryo-ET and subtomogram averaging, I show that two kinds of helical ESCRT-III heterofilaments with different binding geometries scaffold the membrane into this peculiar shape. Cryo-EM on different isolated ESCRT-III filaments confirmed these geometries, allowing us to establish a theoretical description of the membrane tube and to extract mechanical parameters for the protein filaments. This findings give an interesting insight in how changing filament geometries can translate into different membrane geometries. I will also present plans for the refinement of the structures of these and other isolated ESCRT-III filaments and comparison of the changes in their architecture to the changes in membrane shapes they generate. As it is so far uncertain whether the macromolecular ESCRT-III assemblies formed in vitro are relevant for their physiological function, I also want to compare them with each other: I want to use a simple system of viral egress to compare virions formed in vitro and in cultured cells, and their respective ESCRT-III recruitment and architecture. As in the current work, collaborations with experts in theoretical descriptions and molecular modeling are needed to validate a consensus mechanism for ESCRT-III-mediated membrane fission.

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