6NZZ

LRRC8A-DCPIB in MSP1E3D1 nanodisc expanded state

6NZZ の概要

• エントリーDOI: 10.2210/pdb6nzz/pdb
• 関連するPDBエントリー: 6NZW
• EMDBエントリー: 0562 0563
• 分子名称: Volume-regulated anion channel subunit LRRC8A, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, 4-{[(2S)-2-butyl-6,7-dichloro-2-cyclopentyl-1-oxo-2,3-dihydro-1H-inden-5-yl]oxy}butanoic acid (3 entities in total)
• 機能のキーワード: ion channel, volume-regulation, membrane protein
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 585996.10

構造登録者

Kern, D.M.,Hite, R.K.,Brohawn, S.G. (登録日: 2019-02-14, 公開日: 2019-02-27, 最終更新日: 2025-05-28)

主引用文献

Kern, D.M.,Oh, S.,Hite, R.K.,Brohawn, S.G.
Cryo-EM structures of the DCPIB-inhibited volume-regulated anion channel LRRC8A in lipid nanodiscs.
Elife, 8:-, 2019

PubMed Abstract: Hypoosmotic conditions activate volume-regulated anion channels in vertebrate cells. These channels are formed by leucine-rich repeat-containing protein 8 (LRRC8) family members and contain LRRC8A in homo- or hetero-hexameric assemblies. Here, we present single-particle cryo-electron microscopy structures of LRRC8A in complex with the inhibitor DCPIB reconstituted in lipid nanodiscs. DCPIB plugs the channel like a cork in a bottle - binding in the extracellular selectivity filter and sterically occluding ion conduction. Constricted and expanded structures reveal coupled dilation of cytoplasmic LRRs and the channel pore, suggesting a mechanism for channel gating by internal stimuli. Conformational and symmetry differences between LRRC8A structures determined in detergent micelles and lipid bilayers related to reorganization of intersubunit lipid binding sites demonstrate a critical role for the membrane in determining channel structure. These results provide insight into LRRC8 gating and inhibition and the role of lipids in the structure of an ionic-strength sensing ion channel.

PubMed: 30775971
DOI: 10.7554/eLife.42636

実験手法

ELECTRON MICROSCOPY (3.32 Å)