8F79

LRRC8A(T48D):C conformation 2 top focus

8F79 の概要

• エントリーDOI: 10.2210/pdb8f79/pdb
• 関連するPDBエントリー: 8F74 8F75 8F77 8F7B 8F7D 8F7E 8F7J
• EMDBエントリー: 28894 28895 28897 28898 28901 28903 28904 28905
• 分子名称: Volume-regulated anion channel subunit LRRC8A,Soluble cytochrome b562, Volume-regulated anion channel subunit LRRC8C, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, ... (4 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 (house mouse); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 633993.60

構造登録者

Kern, D.M.,Brohawn, S.G. (登録日: 2022-11-18, 公開日: 2023-03-08, 最終更新日: 2023-07-05)

主引用文献

Kern, D.M.,Bleier, J.,Mukherjee, S.,Hill, J.M.,Kossiakoff, A.A.,Isacoff, E.Y.,Brohawn, S.G.
Structural basis for assembly and lipid-mediated gating of LRRC8A:C volume-regulated anion channels.
Nat.Struct.Mol.Biol., 30:841-852, 2023

PubMed Abstract: Leucine-rich repeat-containing protein 8 (LRRC8) family members form volume-regulated anion channels activated by hypoosmotic cell swelling. LRRC8 channels are ubiquitously expressed in vertebrate cells as heteromeric assemblies of LRRC8A (SWELL1) and LRRC8B-E subunits. Channels of different subunit composition have distinct properties that explain the functional diversity of LRRC8 currents across cell types. However, the basis for heteromeric LRRC8 channel assembly and function is unknown. Here we leverage a fiducial-tagging strategy to determine single-particle cryo-EM structures of heterohexameric LRRC8A:C channels in multiple conformations. Compared to homomers, LRRC8A:C channels show pronounced differences in architecture due to heterotypic LRR interactions that displace subunits away from the conduction axis and poise the channel for activation. Structures and functional studies further reveal that lipids embedded in the channel pore block ion conduction in the closed state. These results provide insight into determinants for heteromeric LRRC8 channel assembly, activity and gating by lipids.

PubMed: 36928458
DOI: 10.1038/s41594-023-00944-6

実験手法

ELECTRON MICROSCOPY (3.15 Å)