登録情報 データベース : EMDB / ID : EMD-29082 ダウンロードとリンクタイトル Cryo-EM structure of human voltage-gated sodium channel Nav1.6 マップデータCryo-EM structure of human voltage-gated sodium channel Nav1.6 詳細 試料複合体 : Complex of human voltage-gated sodium channel Nav1.6 with auxiliary beta-1 subunitタンパク質・ペプチド : Sodium channel protein type 8 subunit alphaタンパク質・ペプチド : Sodium channel subunit beta-1リガンド : 2-acetamido-2-deoxy-beta-D-glucopyranoseリガンド : CHOLESTEROL HEMISUCCINATEリガンド : CHOLESTEROLリガンド : 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINEリガンド : 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINEリガンド : O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serineリガンド : (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-enリガンド : (5E,17R,20S)-23-amino-20-hydroxy-14,20-dioxo-15,19,21-trioxa-20lambda~5~-phosphatricos-5-en-17-yl hexadecanoate 残り5件を表示 表示を減らす 詳細 キーワード Voltage-gated sodium channel / Nav1.6 / 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 / membrane depolarization during Purkinje myocyte cell action potential / regulation of atrial cardiac muscle cell membrane depolarization / sodium ion binding / cardiac conduction / membrane depolarization during cardiac muscle cell action potential / membrane depolarization during action potential / positive regulation of sodium ion transport / regulation of sodium ion transmembrane transport ... corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / membrane depolarization during Purkinje myocyte cell action potential / regulation of atrial cardiac muscle cell membrane depolarization / sodium ion binding / cardiac conduction / membrane depolarization during cardiac muscle cell action potential / membrane depolarization during action potential / positive regulation of sodium ion transport / regulation of sodium ion transmembrane transport / peripheral nervous system development / axon initial segment / regulation of ventricular cardiac muscle cell membrane repolarization / cardiac muscle cell action potential involved in contraction / locomotion / node of Ranvier / voltage-gated sodium channel complex / sodium channel inhibitor activity / neuronal action potential propagation / Interaction between L1 and Ankyrins / podosome / anchoring junction / voltage-gated sodium channel activity / sodium ion transport / Phase 0 - rapid depolarisation / regulation of heart rate by cardiac conduction / action potential / intercalated disc / membrane depolarization / sodium channel regulator activity / cardiac muscle contraction / myelination / T-tubule / sodium ion transmembrane transport / axon guidance / positive regulation of neuron projection development / Z disc / Sensory perception of sweet, bitter, and umami (glutamate) taste / cell junction / cytoplasmic vesicle / perikaryon / transmembrane transporter binding / cell adhesion / axon / extracellular region / membrane / plasma membrane 類似検索 - 分子機能 Voltage gated sodium channel, alpha-8 subunit / Sodium channel subunit beta-1/beta-3 / 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 ... Voltage gated sodium channel, alpha-8 subunit / Sodium channel subunit beta-1/beta-3 / 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 / IQ motif profile. / Voltage-dependent channel domain superfamily / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Ion transport domain / Ion transport protein / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold 類似検索 - ドメイン・相同性 Sodium channel regulatory subunit beta-1 / Sodium channel protein type 8 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 : 3.1 Å 詳細 データ登録者Fan X / Huang J / Yan N 資金援助 フランス, 1件 詳細 詳細を隠すOrganization Grant number 国 Human Frontier Science Program (HFSP) LT000754 フランス
引用ジャーナル : Proc Natl Acad Sci U S A / 年 : 2023タイトル : Cryo-EM structure of human voltage-gated sodium channel Na1.6.著者 : Xiao Fan / Jian Huang / Xueqin Jin / Nieng Yan / 要旨 : Voltage-gated sodium channel Na1.6 plays a crucial role in neuronal firing in the central nervous system (CNS). Aberrant function of Na1.6 may lead to epilepsy and other neurological disorders. ... Voltage-gated sodium channel Na1.6 plays a crucial role in neuronal firing in the central nervous system (CNS). Aberrant function of Na1.6 may lead to epilepsy and other neurological disorders. Specific inhibitors of Na1.6 thus have therapeutic potentials. Here we present the cryo-EM structure of human Na1.6 in the presence of auxiliary subunits β1 and fibroblast growth factor homologous factor 2B (FHF2B) at an overall resolution of 3.1 Å. The overall structure represents an inactivated state with closed pore domain (PD) and all "up" voltage-sensing domains. A conserved carbohydrate-aromatic interaction involving Trp302 and Asn326, together with the β1 subunit, stabilizes the extracellular loop in repeat I. Apart from regular lipids that are resolved in the EM map, an unprecedented Y-shaped density that belongs to an unidentified molecule binds to the PD, revealing a potential site for developing Na1.6-specific blockers. Structural mapping of disease-related Na1.6 mutations provides insights into their pathogenic mechanism. 履歴 登録 2022年12月14日 - ヘッダ(付随情報) 公開 2023年2月8日 - マップ公開 2023年2月8日 - 更新 2024年11月13日 - 現状 2024年11月13日 処理サイト : RCSB / 状態 : 公開
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