8QBF

Compact state - Pil1 dimer with lipid headgroups fitted in native eisosome lattice bound to plasma membrane microdomain

8QBF の概要

• エントリーDOI: 10.2210/pdb8qbf/pdb
• EMDBエントリー: 18311
• 分子名称: Sphingolipid long chain base-responsive protein PIL1, D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE, PHOSPHOSERINE (3 entities in total)
• 機能のキーワード: bar domain, lipid reconstitution, membrane microdomain, lipid binding protein
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62202.85

構造登録者

Kefauver, J.M.,Zou, L.,Desfosses, A.,Loewith, R.J. (登録日: 2023-08-24, 公開日: 2024-07-24, 最終更新日: 2024-08-28)

主引用文献

Kefauver, J.M.,Hakala, M.,Zou, L.,Alba, J.,Espadas, J.,Tettamanti, M.G.,Gajic, J.,Gabus, C.,Campomanes, P.,Estrozi, L.F.,Sen, N.E.,Vanni, S.,Roux, A.,Desfosses, A.,Loewith, R.
Cryo-EM architecture of a near-native stretch-sensitive membrane microdomain.
Nature, 632:664-671, 2024

PubMed Abstract: Biological membranes are partitioned into functional zones termed membrane microdomains, which contain specific lipids and proteins. The composition and organization of membrane microdomains remain controversial because few techniques are available that allow the visualization of lipids in situ without disrupting their native behaviour. The yeast eisosome, composed of the BAR-domain proteins Pil1 and Lsp1 (hereafter, Pil1/Lsp1), scaffolds a membrane compartment that senses and responds to mechanical stress by flattening and releasing sequestered factors. Here we isolated near-native eisosomes as helical tubules made up of a lattice of Pil1/Lsp1 bound to plasma membrane lipids, and solved their structures by helical reconstruction. Our structures reveal a striking organization of membrane lipids, and, using in vitro reconstitutions and molecular dynamics simulations, we confirmed the positioning of individual PI(4,5)P, phosphatidylserine and sterol molecules sequestered beneath the Pil1/Lsp1 coat. Three-dimensional variability analysis of the native-source eisosomes revealed a dynamic stretching of the Pil1/Lsp1 lattice that affects the sequestration of these lipids. Collectively, our results support a mechanism in which stretching of the Pil1/Lsp1 lattice liberates lipids that would otherwise be anchored by the Pil1/Lsp1 coat, and thus provide mechanistic insight into how eisosome BAR-domain proteins create a mechanosensitive membrane microdomain.

PubMed: 39048819
DOI: 10.1038/s41586-024-07720-6

実験手法

ELECTRON MICROSCOPY (3.67 Å)