6P6X

Crystal structure of voltage-gated sodium channel NavAb G94C/Q150C mutant in the activated state

6P6X の概要

• エントリーDOI: 10.2210/pdb6p6x/pdb
• 分子名称: Ion transport protein, 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, 3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE (3 entities in total)
• 機能のキーワード: ion channel, ion transport protein, membrane protein, metal transport
• 由来する生物種: Arcobacter butzleri (strain RM4018)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37150.61

構造登録者

Wisedchaisri, G.,Tonggu, L.,McCord, E.,Gamal El-Din, T.M.,Wang, L.,Zheng, N.,Catterall, W.A. (登録日: 2019-06-04, 公開日: 2019-08-14, 最終更新日: 2023-10-11)

主引用文献

Wisedchaisri, G.,Tonggu, L.,McCord, E.,Gamal El-Din, T.M.,Wang, L.,Zheng, N.,Catterall, W.A.
Resting-State Structure and Gating Mechanism of a Voltage-Gated Sodium Channel.
Cell, 178:993-, 2019

PubMed Abstract: Voltage-gated sodium (Na) channels initiate action potentials in nerve, muscle, and other electrically excitable cells. The structural basis of voltage gating is uncertain because the resting state exists only at deeply negative membrane potentials. To stabilize the resting conformation, we inserted voltage-shifting mutations and introduced a disulfide crosslink in the VS of the ancestral bacterial sodium channel NaAb. Here, we present a cryo-EM structure of the resting state and a complete voltage-dependent gating mechanism. The S4 segment of the VS is drawn intracellularly, with three gating charges passing through the transmembrane electric field. This movement forms an elbow connecting S4 to the S4-S5 linker, tightens the collar around the S6 activation gate, and prevents its opening. Our structure supports the classical "sliding helix" mechanism of voltage sensing and provides a complete gating mechanism for voltage sensor function, pore opening, and activation-gate closure based on high-resolution structures of a single sodium channel protein.

PubMed: 31353218
DOI: 10.1016/j.cell.2019.06.031

実験手法

X-RAY DIFFRACTION (2.75 Å)