6DJB

Structure of human Volume Regulated Anion Channel composed of SWELL1 (LRRC8A)

6DJB の概要

• エントリーDOI: 10.2210/pdb6djb/pdb
• EMDBエントリー: 7935
• 分子名称: Volume-regulated anion channel subunit LRRC8A (1 entity in total)
• 機能のキーワード: anion channel, lrrc8a, swell1, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 565911.10

構造登録者

Kefauver, J.M.,Saotome, K.,Pallesen, J.,Cottrell, C.A.,Ward, A.B.,Patapoutian, A. (登録日: 2018-05-24, 公開日: 2018-08-15, 最終更新日: 2024-10-23)

主引用文献

Kefauver, J.M.,Saotome, K.,Dubin, A.E.,Pallesen, J.,Cottrell, C.A.,Cahalan, S.M.,Qiu, Z.,Hong, G.,Crowley, C.S.,Whitwam, T.,Lee, W.H.,Ward, A.B.,Patapoutian, A.
Structure of the human volume regulated anion channel.
Elife, 7:-, 2018

PubMed Abstract: SWELL1 (LRRC8A) is the only essential subunit of the Volume Regulated Anion Channel (VRAC), which regulates cellular volume homeostasis and is activated by hypotonic solutions. SWELL1, together with four other LRRC8 family members, potentially forms a vastly heterogeneous cohort of VRAC channels with different properties; however, SWELL1 alone is also functional. Here, we report a high-resolution cryo-electron microscopy structure of full-length human homo-hexameric SWELL1. The structure reveals a trimer of dimers assembly with symmetry mismatch between the pore-forming domain and the cytosolic leucine-rich repeat (LRR) domains. Importantly, mutational analysis demonstrates that a charged residue at the narrowest constriction of the homomeric channel is an important pore determinant of heteromeric VRAC. Additionally, a mutation in the flexible N-terminal portion of SWELL1 affects pore properties, suggesting a putative link between intracellular structures and channel regulation. This structure provides a scaffold for further dissecting the heterogeneity and mechanism of activation of VRAC.

PubMed: 30095067
DOI: 10.7554/eLife.38461

実験手法

ELECTRON MICROSCOPY (4.4 Å)