登録情報 データベース : EMDB / ID : EMD-29665 ダウンロードとリンクタイトル Cryo-EM structure of Nav1.7 with CBD マップデータ 詳細 試料複合体 : Human voltage-gated sodium channel Nav1.7 with beta subunitsタンパク質・ペプチド : Sodium channel protein type 9 subunit alphaタンパク質・ペプチド : Sodium channel subunit beta-1タンパク質・ペプチド : Sodium channel subunit beta-2リガンド : 2-acetamido-2-deoxy-beta-D-glucopyranoseリガンド : cannabidiolリガンド : O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serineリガンド : CHOLESTEROL HEMISUCCINATEリガンド : (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-enリガンド : 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINEリガンド : 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE 残り4件を表示 表示を減らす 詳細 キーワード Cryo-EM / sodium channel / VGSC / Nav1.7 / CBD / 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 / sensory perception of pain / T-tubule / 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 / SCN5A-like, C-terminal IQ motif / Sodium ion transport-associated / Voltage-gated sodium channel alpha subunit, inactivation gate / Sodium ion transport-associated / 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 / SCN5A-like, C-terminal IQ motif / Sodium ion transport-associated / Voltage-gated sodium channel alpha subunit, inactivation gate / Sodium ion transport-associated / 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 : 2.8 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) フランス
引用ジャーナル : Nat Commun / 年 : 2023タイトル : Cannabidiol inhibits Na channels through two distinct binding sites.著者 : Jian Huang / Xiao Fan / Xueqin Jin / Sooyeon Jo / Hanxiong Bear Zhang / Akie Fujita / Bruce P Bean / Nieng Yan / 要旨 : Cannabidiol (CBD), a major non-psychoactive phytocannabinoid in cannabis, is an effective treatment for some forms of epilepsy and pain. At high concentrations, CBD interacts with a huge variety of ... Cannabidiol (CBD), a major non-psychoactive phytocannabinoid in cannabis, is an effective treatment for some forms of epilepsy and pain. At high concentrations, CBD interacts with a huge variety of proteins, but which targets are most relevant for clinical actions is still unclear. Here we show that CBD interacts with Na1.7 channels at sub-micromolar concentrations in a state-dependent manner. Electrophysiological experiments show that CBD binds to the inactivated state of Na1.7 channels with a dissociation constant of about 50 nM. The cryo-EM structure of CBD bound to Na1.7 channels reveals two distinct binding sites. One is in the IV-I fenestration near the upper pore. The other binding site is directly next to the inactivated "wedged" position of the Ile/Phe/Met (IFM) motif on the short linker between repeats III and IV, which mediates fast inactivation. Consistent with producing a direct stabilization of the inactivated state, mutating residues in this binding site greatly reduced state-dependent binding of CBD. The identification of this binding site may enable design of compounds with improved properties compared to CBD itself. 履歴 登録 2023年2月1日 - ヘッダ(付随情報) 公開 2023年7月5日 - マップ公開 2023年7月5日 - 更新 2025年5月14日 - 現状 2025年5月14日 処理サイト : RCSB / 状態 : 公開
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