Biophysical Society Thematic Meeting| Padova 2019

Quantitative Aspects of Membrane Fusion and Fission

Poster Abstracts

36-POS Board 36 STRUCTURAL STUDIES OF MEMBRANES CONSTRICTED BY ESCRT-III PROTEINS Frank R. Moss 1 ; Henry Nguyen 1 ; Adam Frost 1 ; 1 University of California, San Francisco, Biochemistry and Biophysics, San Francisco, California, USA Fission of biological membranes is an essential process that maintains their necessary shapes, sizes, compositions, and connectivity. Additionally, pathogens must hijack membrane fission pathways to infect and escape from cells. Despite its importance, many aspects of fission remain poorly understood, including how fission proteins assemble on membranes and convert chemical energy to the mechanical force needed to sever lipid bilayers. I have utilized a combination of chemical synthesis, biophysics, cryo-electron microscopy (cryo-EM), and molecular dynamics simulations to investigate how one class of fission proteins (ESCRT-III) remodels membranes and alters the physical properties of lipid bilayers to effect fission. Cryo-EM reconstructions of ESCRT-III-bound membranes with brominated analogs of lipids, which strongly scatter electrons, reveal lipid leaflet asymmetry induced by high curvature and molecular details of lipid packing. The structures of ESCRT-III proteins assembled on membranes containing brominated lipids provide insight into how the proteins are able to alter the structure membranes to overcome the energetic barrier to fission. Finally, we compare experimental results to calculations using continuum models in order to shed light on how these structures lead to fission. An improved understanding of the mechanism of membrane fission could provide new therapeutic targets for diseases and infections involving malfunctioning membrane-remodeling proteins.

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