6M04

Structure of the human homo-hexameric LRRC8D channel at 4.36 Angstroms

6M04 の概要

• エントリーDOI: 10.2210/pdb6m04/pdb
• EMDBエントリー: 30029
• 分子名称: Volume-regulated anion channel subunit LRRC8D (1 entity in total)
• 機能のキーワード: ion channel, 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: 595867.08

構造登録者

Nakamura, R.,Kasuya, G.,Yokoyama, T.,Shirouzu, M.,Ishitani, R.,Nureki, O. (登録日: 2020-02-20, 公開日: 2020-06-17, 最終更新日: 2024-10-09)

主引用文献

Nakamura, R.,Numata, T.,Kasuya, G.,Yokoyama, T.,Nishizawa, T.,Kusakizako, T.,Kato, T.,Hagino, T.,Dohmae, N.,Inoue, M.,Watanabe, K.,Ichijo, H.,Kikkawa, M.,Shirouzu, M.,Jentsch, T.J.,Ishitani, R.,Okada, Y.,Nureki, O.
Cryo-EM structure of the volume-regulated anion channel LRRC8D isoform identifies features important for substrate permeation.
Commun Biol, 3:240-240, 2020

PubMed Abstract: Members of the leucine-rich repeat-containing 8 (LRRC8) protein family, composed of the five LRRC8A-E isoforms, are pore-forming components of the volume-regulated anion channel (VRAC). LRRC8A and at least one of the other LRRC8 isoforms assemble into heteromers to generate VRAC transport activities. Despite the availability of the LRRC8A structures, the structural basis of how LRRC8 isoforms other than LRRC8A contribute to the functional diversity of VRAC has remained elusive. Here, we present the structure of the human LRRC8D isoform, which enables the permeation of organic substrates through VRAC. The LRRC8D homo-hexamer structure displays a two-fold symmetric arrangement, and together with a structure-based electrophysiological analysis, revealed two key features. The pore constriction on the extracellular side is wider than that in the LRRC8A structures, which may explain the increased permeability of organic substrates. Furthermore, an N-terminal helix protrudes into the pore from the intracellular side and may be critical for gating.

PubMed: 32415200
DOI: 10.1038/s42003-020-0951-z

実験手法

ELECTRON MICROSCOPY (4.36 Å)