bundle of His cell action potential / AV node cell action potential / clathrin complex / regulation of atrial cardiac muscle cell membrane depolarization / sensory perception / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / membrane depolarization during action potential / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel complex / regulation of monoatomic ion transmembrane transport ...bundle of His cell action potential / AV node cell action potential / clathrin complex / regulation of atrial cardiac muscle cell membrane depolarization / sensory perception / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / membrane depolarization during action potential / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel complex / regulation of monoatomic ion transmembrane transport / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / Phase 0 - rapid depolarisation / odontogenesis of dentin-containing tooth / regulation of cardiac muscle contraction / sodium ion transmembrane transport / regulation of heart rate / presynaptic membrane / transmembrane transporter binding / axon / glutamatergic synapse / extracellular exosome / plasma membrane 類似検索 - 分子機能
Voltage-gated sodium channel alpha subunit, inactivation gate / Sodium ion transport-associated / Sodium ion transport-associated / Voltage gated sodium channel, alpha subunit / Voltage-gated cation channel calcium and sodium / Voltage-dependent channel domain superfamily / Ion transport domain / Ion transport protein 類似検索 - ドメイン・相同性
Sodium channel protein type 10 subunit alpha 類似検索 - 構成要素
ジャーナル: Proc Natl Acad Sci U S A / 年: 2022 タイトル: Structural basis for high-voltage activation and subtype-specific inhibition of human Na1.8. 著者: Xiaoshuang Huang / Xueqin Jin / Gaoxingyu Huang / Jian Huang / Tong Wu / Zhangqiang Li / Jiaofeng Chen / Fang Kong / Xiaojing Pan / Nieng Yan / 要旨: The dorsal root ganglia-localized voltage-gated sodium (Na) channel Na1.8 represents a promising target for developing next-generation analgesics. A prominent characteristic of Na1.8 is the ...The dorsal root ganglia-localized voltage-gated sodium (Na) channel Na1.8 represents a promising target for developing next-generation analgesics. A prominent characteristic of Na1.8 is the requirement of more depolarized membrane potential for activation. Here we present the cryogenic electron microscopy structures of human Na1.8 alone and bound to a selective pore blocker, A-803467, at overall resolutions of 2.7 to 3.2 Å. The first voltage-sensing domain (VSD) displays three different conformations. Structure-guided mutagenesis identified the extracellular interface between VSD and the pore domain (PD) to be a determinant for the high-voltage dependence of activation. A-803467 was clearly resolved in the central cavity of the PD, clenching S6. Our structure-guided functional characterizations show that two nonligand binding residues, Thr397 on S6 and Gly1406 on S6, allosterically modulate the channel's sensitivity to A-803467. Comparison of available structures of human Na channels suggests the extracellular loop region to be a potential site for developing subtype-specific pore-blocking biologics.