5IS0

Structure of TRPV1 in complex with capsazepine, determined in lipid nanodisc

5IS0 の概要

• エントリーDOI: 10.2210/pdb5is0/pdb
• 関連するPDBエントリー: 5IRX 5IRZ
• EMDBエントリー: 8117 8118 8119 8120
• 分子名称: Transient receptor potential cation channel subfamily V member 1, capsazepine (2 entities in total)
• 機能のキーワード: trp, ion channel, nanodisc, vanilloid, lipid, interaction, transport protein
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 293344.79

構造登録者

Gao, Y.,Cao, E.,Julius, D.,Cheng, Y. (登録日: 2016-03-15, 公開日: 2016-05-25, 最終更新日: 2024-03-06)

主引用文献

Gao, Y.,Cao, E.,Julius, D.,Cheng, Y.
TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action.
Nature, 534:347-351, 2016

PubMed Abstract: When integral membrane proteins are visualized in detergents or other artificial systems, an important layer of information is lost regarding lipid interactions and their effects on protein structure. This is especially relevant to proteins for which lipids have both structural and regulatory roles. Here we demonstrate the power of combining electron cryo-microscopy with lipid nanodisc technology to ascertain the structure of the rat TRPV1 ion channel in a native bilayer environment. Using this approach, we determined the locations of annular and regulatory lipids and showed that specific phospholipid interactions enhance binding of a spider toxin to TRPV1 through formation of a tripartite complex. Furthermore, phosphatidylinositol lipids occupy the binding site for capsaicin and other vanilloid ligands, suggesting a mechanism whereby chemical or thermal stimuli elicit channel activation by promoting the release of bioactive lipids from a critical allosteric regulatory site.

PubMed: 27281200
DOI: 10.1038/nature17964

実験手法

ELECTRON MICROSCOPY (3.43 Å)