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-Structure paper
タイトル | Structure of the Cardiac Sodium Channel. |
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ジャーナル・号・ページ | Cell, Vol. 180, Issue 1, Page 122-134.e10, Year 2020 |
掲載日 | 2020年1月9日 |
著者 | Daohua Jiang / Hui Shi / Lige Tonggu / Tamer M Gamal El-Din / Michael J Lenaeus / Yan Zhao / Craig Yoshioka / Ning Zheng / William A Catterall / |
PubMed 要旨 | 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 ...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. |
リンク | Cell / PubMed:31866066 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.24 - 3.5 Å |
構造データ | EMDB-20949, PDB-6uz0: EMDB-20951, PDB-6uz3: |
化合物 | ChemComp-NAG: ChemComp-9Z9: ChemComp-6OU: ChemComp-K4D: |
由来 |
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キーワード | METAL TRANSPORT / Cardiac sodium channel complex with flecainide / ion channel (イオンチャネル) / cardiac sodium channel |