8BEN

LRR domain Structure of the LRRC8C protein

8BEN の概要

• エントリーDOI: 10.2210/pdb8ben/pdb
• 関連するPDBエントリー: 8B40 8B41 8B42
• EMDBエントリー: 15835 15836 15837 15838 15839 15840 15841
• 分子名称: Volume-regulated anion channel subunit LRRC8C (1 entity in total)
• 機能のキーワード: ion channel, volume-regulated anion channel, membrane protein
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 188756.38

構造登録者

Sawicka, M.,Dutzler, R. (登録日: 2022-10-21, 公開日: 2022-12-14, 最終更新日: 2024-02-07)

主引用文献

Rutz, S.,Deneka, D.,Dittmann, A.,Sawicka, M.,Dutzler, R.
Structure of a volume-regulated heteromeric LRRC8A/C channel.
Nat.Struct.Mol.Biol., 30:52-61, 2023

PubMed Abstract: Volume-regulated anion channels (VRACs) participate in the cellular response to osmotic swelling. These membrane proteins consist of heteromeric assemblies of LRRC8 subunits, whose compositions determine permeation properties. Although structures of the obligatory LRRC8A, also referred to as SWELL1, have previously defined the architecture of VRACs, the organization of heteromeric channels has remained elusive. Here we have addressed this question by the structural characterization of murine LRRC8A/C channels. Like LRRC8A, these proteins assemble as hexamers. Despite 12 possible arrangements, we find a predominant organization with an A:C ratio of two. In this assembly, four LRRC8A subunits cluster in their preferred conformation observed in homomers, as pairs of closely interacting proteins that stabilize a closed state of the channel. In contrast, the two interacting LRRC8C subunits show a larger flexibility, underlining their role in the destabilization of the tightly packed A subunits, thereby enhancing the activation properties of the protein.

PubMed: 36522427
DOI: 10.1038/s41594-022-00899-0

実験手法

X-RAY DIFFRACTION (3.1 Å)