7FBS

structure of a channel

Summary for 7FBS

• Entry DOI: 10.2210/pdb7fbs/pdb
• EMDB information: 31519
• Descriptor: Sodium channel protein type 5 subunit alpha,Sodium channel protein type 5 subunit alpha,Sodium channel protein type 5 subunit alpha,G protein/GFP fusion protein, 2-acetamido-2-deoxy-beta-D-glucopyranose, [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate, ... (5 entities in total)
• Functional Keywords: ion channel, four-domain, membrane protein
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 1
• Total formula weight: 219023.26

Authors

Jiang, D.J.,Catterall, W.A. (deposition date: 2021-07-12, release date: 2021-09-22, Last modification date: 2025-07-02)

Primary citation

Jiang, D.,Banh, R.,Gamal El-Din, T.M.,Tonggu, L.,Lenaeus, M.J.,Pomes, R.,Zheng, N.,Catterall, W.A.
Open-state structure and pore gating mechanism of the cardiac sodium channel.
Cell, 184:5151-, 2021

PubMed Abstract: The heartbeat is initiated by voltage-gated sodium channel Na1.5, which opens rapidly and triggers the cardiac action potential; however, the structural basis for pore opening remains unknown. Here, we blocked fast inactivation with a mutation and captured the elusive open-state structure. The fast inactivation gate moves away from its receptor, allowing asymmetric opening of pore-lining S6 segments, which bend and rotate at their intracellular ends to dilate the activation gate to ∼10 Å diameter. Molecular dynamics analyses predict physiological rates of Na conductance. The open-state pore blocker propafenone binds in a high-affinity pose, and drug-access pathways are revealed through the open activation gate and fenestrations. Comparison with mutagenesis results provides a structural map of arrhythmia mutations that target the activation and fast inactivation gates. These results give atomic-level insights into molecular events that underlie generation of the action potential, open-state drug block, and fast inactivation of cardiac sodium channels, which initiate the heartbeat.

PubMed: 34520724
DOI: 10.1016/j.cell.2021.08.021

Experimental method

ELECTRON MICROSCOPY (3.4 Å)