6UZ3

Cardiac sodium channel

Summary for 6UZ3

• Entry DOI: 10.2210/pdb6uz3/pdb
• EMDB information: 20949 20951
• Descriptor: Sodium channel protein type 5 subunit alpha,Green fluorescent protein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: cardiac sodium channel, ion channel, metal transport
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 1
• Total formula weight: 221537.52

Authors

Jiang, D.,Shi, H.,Tonggu, L.,Lenaeus, M.J.,Zheng, N.,Catterall, W.A. (deposition date: 2019-11-14, release date: 2020-01-01, Last modification date: 2024-10-16)

Primary citation

Jiang, D.,Shi, H.,Tonggu, L.,Gamal El-Din, T.M.,Lenaeus, M.J.,Zhao, Y.,Yoshioka, C.,Zheng, N.,Catterall, W.A.
Structure of the Cardiac Sodium Channel.
Cell, 180:122-134.e10, 2020

PubMed Abstract: Voltage-gated sodium channel Na1.5 generates cardiac action potentials and initiates the heartbeat. Here, we report structures of Na1.5 at 3.2-3.5 Å resolution. Na1.5 is distinguished from other sodium channels by a unique glycosyl moiety and loss of disulfide-bonding capability at the Naβ subunit-interaction sites. The antiarrhythmic drug flecainide specifically targets the central cavity of the pore. The voltage sensors are partially activated, and the fast-inactivation gate is partially closed. Activation of the voltage sensor of Domain III allows binding of the isoleucine-phenylalanine-methionine (IFM) motif to the inactivation-gate receptor. Asp and Ala, in the selectivity motif DEKA, line the walls of the ion-selectivity filter, whereas Glu and Lys are in positions to accept and release Na ions via a charge-delocalization network. Arrhythmia mutation sites undergo large translocations during gating, providing a potential mechanism for pathogenic effects. Our results provide detailed insights into Na1.5 structure, pharmacology, activation, inactivation, ion selectivity, and arrhythmias.

PubMed: 31866066
DOI: 10.1016/j.cell.2019.11.041

Experimental method

ELECTRON MICROSCOPY (3.5 Å)