+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-29665 | |||||||||
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タイトル | Cryo-EM structure of Nav1.7 with CBD | |||||||||
マップデータ | ||||||||||
試料 |
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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 corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / detection of mechanical stimulus involved in sensory perception / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / membrane depolarization during Purkinje myocyte cell action potential / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / regulation of atrial cardiac muscle cell membrane depolarization ...corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / detection of mechanical stimulus involved in sensory perception / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / membrane depolarization during Purkinje myocyte cell action potential / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / regulation of atrial cardiac muscle cell membrane depolarization / cardiac conduction / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / node of Ranvier / sodium channel inhibitor activity / cardiac muscle cell action potential involved in contraction / locomotion / membrane depolarization during action potential / voltage-gated sodium channel complex / regulation of ventricular cardiac muscle cell membrane repolarization / neuronal action potential propagation / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / sodium ion transport / behavioral response to pain / Phase 0 - rapid depolarisation / regulation of heart rate by cardiac conduction / detection of temperature stimulus involved in sensory perception of pain / membrane depolarization / intercalated disc / sodium ion transmembrane transport / sodium channel regulator activity / cardiac muscle contraction / T-tubule / sensory perception of pain / post-embryonic development / axon guidance / positive regulation of neuron projection development / response to toxic substance / Sensory perception of sweet, bitter, and umami (glutamate) taste / circadian rhythm / nervous system development / gene expression / response to heat / 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 | |||||||||
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 | |||||||||
データ登録者 | Fan X / Huang J / Yan N | |||||||||
資金援助 | フランス, 1件
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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 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_29665.map.gz | 118 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-29665-v30.xml emd-29665.xml | 19.9 KB 19.9 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_29665_fsc.xml | 10.5 KB | 表示 | FSCデータファイル |
画像 | emd_29665.png | 173.1 KB | ||
マスクデータ | emd_29665_msk_1.map | 125 MB | マスクマップ | |
その他 | emd_29665_half_map_1.map.gz emd_29665_half_map_2.map.gz | 116 MB 116 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-29665 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29665 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_29665_validation.pdf.gz | 962.4 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_29665_full_validation.pdf.gz | 962 KB | 表示 | |
XML形式データ | emd_29665_validation.xml.gz | 19.1 KB | 表示 | |
CIF形式データ | emd_29665_validation.cif.gz | 24.6 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29665 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29665 | HTTPS FTP |
-関連構造データ
関連構造データ | 8g1aMC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_29665.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.114 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-マスク #1
ファイル | emd_29665_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_29665_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_29665_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : Human voltage-gated sodium channel Nav1.7 with beta subunits
+超分子 #1: Human voltage-gated sodium channel Nav1.7 with beta subunits
+分子 #1: Sodium channel protein type 9 subunit alpha
+分子 #2: Sodium channel subunit beta-1
+分子 #3: Sodium channel subunit beta-2
+分子 #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
+分子 #6: cannabidiol
+分子 #7: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phospho...
+分子 #8: CHOLESTEROL HEMISUCCINATE
+分子 #9: (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]sp...
+分子 #10: 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+分子 #11: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD 最大 デフォーカス(公称値): 1.4000000000000001 µm 最小 デフォーカス(公称値): 1.2 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |