登録情報 データベース : EMDB / ID : EMD-32368 ダウンロードとリンクタイトル Cryo-EM structure of human Nav1.7-beta1-beta2 complex at 2.2 angstrom resolution マップデータ 詳細 試料複合体 : Human voltage-gated sodium channel Nav1.7 in complex with auxiliary beta subunitsリガンド : x 9種 詳細 キーワード Nav1.7 / SCN9A / cryo-EM / MEMBRANE PROTEIN機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / action potential propagation / response to pyrethroid / detection of mechanical stimulus involved in sensory perception / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / membrane depolarization during Purkinje myocyte cell action potential / cardiac conduction / regulation of sodium ion transmembrane transport ... corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / action potential propagation / response to pyrethroid / detection of mechanical stimulus involved in sensory perception / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / membrane depolarization during Purkinje myocyte cell action potential / cardiac conduction / regulation of sodium ion transmembrane transport / regulation of atrial cardiac muscle cell membrane depolarization / membrane depolarization during cardiac muscle cell action potential / membrane depolarization during action potential / positive regulation of sodium ion transport / axon initial segment / cardiac muscle cell action potential involved in contraction / locomotion / regulation of ventricular cardiac muscle cell membrane repolarization / node of Ranvier / voltage-gated sodium channel complex / sodium channel inhibitor activity / neuronal action potential propagation / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / Phase 0 - rapid depolarisation / regulation of heart rate by cardiac conduction / behavioral response to pain / detection of temperature stimulus involved in sensory perception of pain / membrane depolarization / intercalated disc / sodium channel regulator activity / neuronal action potential / cardiac muscle contraction / axon terminus / T-tubule / sensory perception of pain / sodium ion transmembrane transport / axon guidance / post-embryonic development / positive regulation of neuron projection development / response to toxic substance / circadian rhythm / Sensory perception of sweet, bitter, and umami (glutamate) taste / nervous system development / response to heat / gene expression / chemical synaptic transmission / perikaryon / transmembrane transporter binding / cell adhesion / inflammatory response / axon / synapse / extracellular region / plasma membrane 類似検索 - 分子機能 Sodium channel subunit beta-1/beta-3 / Myelin P0 protein-related / Voltage-gated Na+ ion channel, cytoplasmic domain / Cytoplasmic domain of voltage-gated Na+ ion channel / Sodium ion transport-associated / Voltage-gated sodium channel alpha subunit, inactivation gate / Sodium ion transport-associated / SCN5A-like, C-terminal IQ motif / Voltage gated sodium channel, alpha subunit / Voltage-gated cation channel calcium and sodium ... Sodium channel subunit beta-1/beta-3 / Myelin P0 protein-related / Voltage-gated Na+ ion channel, cytoplasmic domain / Cytoplasmic domain of voltage-gated Na+ ion channel / Sodium ion transport-associated / Voltage-gated sodium channel alpha subunit, inactivation gate / Sodium ion transport-associated / SCN5A-like, C-terminal IQ motif / Voltage gated sodium channel, alpha subunit / Voltage-gated cation channel calcium and sodium / Short calmodulin-binding motif containing conserved Ile and Gln residues. / IQ motif, EF-hand binding site / Voltage-dependent channel domain superfamily / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Ion transport domain / Ion transport protein / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold 類似検索 - ドメイン・相同性 Sodium channel regulatory subunit beta-2 / Sodium channel regulatory subunit beta-1 / Sodium channel protein type 9 subunit alpha 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.2 Å 詳細 データ登録者Yan N / Huang G / Liu D / Wei P / Shen H 資金援助 中国, 1件 詳細 詳細を隠すOrganization Grant number 国 Ministry of Science and Technology (MoST, China) 中国
引用ジャーナル : Cell Rep / 年 : 2022タイトル : High-resolution structures of human Na1.7 reveal gating modulation through α-π helical transition of S6.著者 : Gaoxingyu Huang / Dongliang Liu / Weipeng Wang / Qiurong Wu / Jiaofeng Chen / Xiaojing Pan / Huaizong Shen / Nieng Yan / 要旨 : Na1.7 represents a preeminent target for next-generation analgesics for its critical role in pain sensation. Here we report a 2.2-Å resolution cryo-EM structure of wild-type (WT) Na1.7 complexed ... Na1.7 represents a preeminent target for next-generation analgesics for its critical role in pain sensation. Here we report a 2.2-Å resolution cryo-EM structure of wild-type (WT) Na1.7 complexed with the β1 and β2 subunits that reveals several previously indiscernible cytosolic segments. Reprocessing of the cryo-EM data for our reported structures of Na1.7(E406K) bound to various toxins identifies two distinct conformations of S6, one composed of α helical turns only and the other containing a π helical turn in the middle. The structure of ligand-free Na1.7(E406K), determined at 3.5-Å resolution, is identical to the WT channel, confirming that binding of Huwentoxin IV or Protoxin II to VSD allosterically induces the α → π transition of S6. The local secondary structural shift leads to contraction of the intracellular gate, closure of the fenestration on the interface of repeats I and IV, and rearrangement of the binding site for the fast inactivation motif. 履歴 登録 2021年12月9日 - ヘッダ(付随情報) 公開 2022年6月1日 - マップ公開 2022年6月1日 - 更新 2025年6月18日 - 現状 2025年6月18日 処理サイト : PDBj / 状態 : 公開
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