9HHE

Structure of the Ist2 TMEM16 homology domain in the detergent GDN

9HHE の概要

• エントリーDOI: 10.2210/pdb9hhe/pdb
• 関連するPDBエントリー: 9HDH 9HDK
• EMDBエントリー: 52170
• 分子名称: Increased sodium tolerance protein 2 (1 entity in total)
• 機能のキーワード: tmem16 proteins, lipid scramblase, lipid transport, membrane contact sites, tethering protein, membrane 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: 175554.75

構造登録者

Arndt, M.,Dutzler, R. (登録日: 2024-11-21, 公開日: 2025-09-03, 最終更新日: 2025-11-26)

主引用文献

Arndt, M.,Schweri, A.,Dutzler, R.
Structural basis for lipid transport at membrane contact sites by the IST2-OSH6 complex.
Nat.Struct.Mol.Biol., 32:2219-2230, 2025

PubMed Abstract: Membrane contact sites are hubs for interorganellar lipid transport within eukaryotic cells. As a principal tether bridging the endoplasmic reticulum (ER) and the plasma membrane in Saccharomyces cerevisiae, the protein IST2 has a major role during lipid transport between both compartments. Here, we show a comprehensive investigation elucidating the structural and mechanistic properties of IST2 and its interaction with the soluble lipid transfer protein OSH6. The ER-embedded transmembrane domain of IST2 is homologous to the TMEM16 family and acts as a constitutively active lipid scramblase. The extended C terminus binds to the plasma membrane and the phosphatidylserine-phosphatidylinositol 4-phosphate exchanger OSH6. Through cellular growth assays and biochemical and structural studies, we characterized the interaction between both proteins and show that OSH6 remains associated with IST2 during lipid shuttling between membranes. These results highlight the role of the IST2-OSH6 complex in lipid trafficking and offer initial insights into the relevance of scramblases for carrier-like lipid transport mechanisms.

PubMed: 40866577
DOI: 10.1038/s41594-025-01660-z

実験手法

ELECTRON MICROSCOPY (2.84 Å)