6P6W

Cryo-EM structure of voltage-gated sodium channel NavAb N49K/L109A/M116V/G94C/Q150C disulfide crosslinked mutant in the resting state

Summary for 6P6W

• Entry DOI: 10.2210/pdb6p6w/pdb
• EMDB information: 20265
• Descriptor: Fusion of Maltose-binding protein and voltage-gated sodium channel NavAb (1 entity in total)
• Functional Keywords: ion channel, ion transport protein, membrane protein, metal transport
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 4
• Total formula weight: 296291.19

Authors

Wisedchaisri, G.,Tonggu, L.,McCord, E.,Gamal El-Din, T.M.,Wang, L.,Zheng, N.,Catterall, W.A. (deposition date: 2019-06-04, release date: 2019-08-14, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (4 Å)