5VB8

Crystal structure of the NavAb voltage-gated sodium channel in an open state

5VB8 の概要

• エントリーDOI: 10.2210/pdb5vb8/pdb
• 関連するPDBエントリー: 5VB2
• 分子名称: Ion transport protein, SODIUM ION, 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (5 entities in total)
• 機能のキーワード: voltage-gated sodium channel, transport protein
• 由来する生物種: Arcobacter butzleri
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31037.41

構造登録者

Lenaeus, M.J.,Catterall, W.A. (登録日: 2017-03-28, 公開日: 2017-04-05, 最終更新日: 2023-10-04)

主引用文献

Lenaeus, M.J.,Gamal El-Din, T.M.,Ing, C.,Ramanadane, K.,Pomes, R.,Zheng, N.,Catterall, W.A.
Structures of closed and open states of a voltage-gated sodium channel.
Proc. Natl. Acad. Sci. U.S.A., 114:E3051-E3060, 2017

PubMed Abstract: Bacterial voltage-gated sodium channels (BacNavs) serve as models of their vertebrate counterparts. BacNavs contain conserved voltage-sensing and pore-forming domains, but they are homotetramers of four identical subunits, rather than pseudotetramers of four homologous domains. Here, we present structures of two NaAb mutants that capture tightly closed and open states at a resolution of 2.8-3.2 Å. Introduction of two humanizing mutations in the S6 segment (NaAb/FY: T206F and V213Y) generates a persistently closed form of the activation gate in which the intracellular ends of the four S6 segments are drawn tightly together to block ion permeation completely. This construct also revealed the complete structure of the four-helix bundle that forms the C-terminal domain. In contrast, truncation of the C-terminal 40 residues in NaAb/1-226 captures the activation gate in an open conformation, revealing the open state of a BacNav with intact voltage sensors. Comparing these structures illustrates the full range of motion of the activation gate, from closed with its orifice fully occluded to open with an orifice of ∼10 Å. Molecular dynamics and free-energy simulations confirm designation of NaAb/1-226 as an open state that allows permeation of hydrated Na, and these results also support a hydrophobic gating mechanism for control of ion permeation. These two structures allow completion of a closed-open-inactivated conformational cycle in a single voltage-gated sodium channel and give insight into the structural basis for state-dependent binding of sodium channel-blocking drugs.

PubMed: 28348242
DOI: 10.1073/pnas.1700761114

実験手法

X-RAY DIFFRACTION (2.85 Å)