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- W4386203571 abstract "Abstract Biological membranes are partitioned into functional zones containing specific lipids and proteins, termed membrane microdomains. Their composition and organization remain controversial owing to a paucity of techniques that can visualize lipids in situ without disrupting their native behavior 1,2 . The yeast eisosome, a membrane compartment scaffolded by the BAR-domain proteins Pil1 and Lsp1, senses and responds to mechanical stress by flattening and releasing sequestered factors 3–7 . Here, we isolated native eisosomes as helical filaments of Pil1/Lsp1 lattice bound to plasma membrane lipids and solved their structures by helical reconstruction. We observe remarkable organization within the lipid bilayer density from which we could assign headgroups of PI(4,5)P 2 and phosphatidylserine bound to Pil1/Lsp1 and a pattern of membrane voids, signatures of sterols, beneath an amphipathic helix. We verified these assignments using in vitro reconstitutions and molecular dynamics simulations. 3D variability analysis of the native eisosomes revealed a dynamic stretching of the Pil1/Lsp1 lattice that affects functionally important lipid sequestration, supporting a mechanism in which membrane stretching liberates lipids otherwise anchored by the Pil1/Lsp1 coat. Our results provide mechanistic insight into how eisosome BAR-domain proteins create a mechanosensitive membrane microdomain and, more globally, resolve long-standing controversies about the architecture and nature of lipid microdomains." @default.
- W4386203571 created "2023-08-28" @default.
- W4386203571 creator A5001022567 @default.
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- W4386203571 creator A5037403931 @default.
- W4386203571 creator A5044993402 @default.
- W4386203571 creator A5050409486 @default.
- W4386203571 creator A5067041638 @default.
- W4386203571 creator A5075758578 @default.
- W4386203571 creator A5083836716 @default.
- W4386203571 creator A5092703373 @default.
- W4386203571 date "2023-08-26" @default.
- W4386203571 modified "2023-09-25" @default.
- W4386203571 title "CryoEM architecture of a native stretch-sensitive membrane microdomain" @default.
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