8XMO

Voltage-gated sodium channel Nav1.7 variant M4

8XMO の概要

• エントリーDOI: 10.2210/pdb8xmo/pdb
• EMDBエントリー: 38484
• 分子名称: Sodium channel subunit beta-2, Sodium channel protein type 9 subunit alpha, Sodium channel subunit beta-1, ... (7 entities in total)
• 機能のキーワード: voltage-gated sodium channel, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 293414.24

構造登録者

Yan, N.,Li, Z.,Wu, Q.,Huang, G. (登録日: 2023-12-27, 公開日: 2024-03-06, 最終更新日: 2024-11-27)

主引用文献

Li, Z.,Wu, Q.,Huang, G.,Jin, X.,Li, J.,Pan, X.,Yan, N.
Dissection of the structure-function relationship of Na v channels.
Proc.Natl.Acad.Sci.USA, 121:e2322899121-e2322899121, 2024

PubMed Abstract: Voltage-gated sodium channels (Na) undergo conformational shifts in response to membrane potential changes, a mechanism known as the electromechanical coupling. To delineate the structure-function relationship of human Na channels, we have performed systematic structural analysis using human Na1.7 as a prototype. Guided by the structural differences between wild-type (WT) Na1.7 and an eleven mutation-containing variant, designated Na1.7-M11, we generated three additional intermediate mutants and solved their structures at overall resolutions of 2.9-3.4 Å. The mutant with nine-point mutations in the pore domain (PD), named Na1.7-M9, has a reduced cavity volume and a sealed gate, with all voltage-sensing domains (VSDs) remaining up. Structural comparison of WT and Na1.7-M9 pinpoints two residues that may be critical to the tightening of the PD. However, the variant containing these two mutations, Na1.7-M2, or even in combination with two additional mutations in the VSDs, named Na1.7-M4, failed to tighten the PD. Our structural analysis reveals a tendency of PD contraction correlated with the right shift of the static inactivation I-V curves. We predict that the channel in the resting state should have a "tight" PD with down VSDs.

PubMed: 38381792
DOI: 10.1073/pnas.2322899121

実験手法

ELECTRON MICROSCOPY (3.39 Å)