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bioRxiv · 10.1101/2021.08.24.457428

Membrane Constriction by ESCRT-III Proteins Induces Structural Lipid Bilayer Asymmetries

Moss, F. R.·Lincoff, J.·Tucker, M.·Mohammed, A.·Grabe, M.·Frost, A.
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Abstract

Lipids in biological membranes are thought to be functionally organized, but few experimental tools can probe nanoscale membrane structure. Using brominated lipids as contrast probes for cryo-EM and a model ESCRT-III membrane remodeling system, we observed leaflet-level and protein-localized lipid structural patterns within highly constricted and thinned membrane nanotubes. These nanotubes differed markedly from protein-free, flat bilayers in leaflet thickness, lipid diffusion rates, and lipid compositional and conformational asymmetries. Simulations and cryo-EM imaging of brominated SDPC showed how a pair of phenylalanine residues scored the outer leaflet with a helical hydrophobic defect where polyunsaturated docosahexaenoyl (DHA) tails accumulated at the bilayer surface. Combining cryo-EM of halogenated lipids with molecular dynamics thus enables new characterizations of the composition and structure of membranes on molecular length scales. One-Sentence SummaryCryo-EM imaging of halogenated lipids and MD simulations provide molecular-scale insight into constricted bilayer structure.

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Moss, F. R., Lincoff, J., Tucker, M., Mohammed, A., Grabe, M., Frost, A.. 2021-08-25. Membrane Constriction by ESCRT-III Proteins Induces Structural Lipid Bilayer Asymmetries. https://doi.org/10.1101/2021.08.24.457428

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