+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-32371 | |||||||||
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タイトル | Cryo-EM structure of human Nav1.7(E406K) in complex with auxiliary beta subunits, huwentoxin-IV and saxitoxin (S6IV pi helix conformer) | |||||||||
マップデータ | ||||||||||
試料 |
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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 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 / regulation of sodium ion transmembrane transport ...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 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 / regulation of sodium ion transmembrane transport / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / node of Ranvier / sodium channel inhibitor activity / membrane depolarization during action potential / voltage-gated sodium channel complex / cardiac muscle cell action potential involved in contraction / locomotion / 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 channel regulator activity / sodium ion transmembrane transport / cardiac muscle contraction / T-tubule / sensory perception of pain / post-embryonic development / axon guidance / response to toxic substance / positive regulation of neuron projection development / 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: 2.9 Å | |||||||||
データ登録者 | Yan N / Huang G / Liu D / Wei P / Shen H | |||||||||
資金援助 | 中国, 1件
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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 |
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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_32371.map.gz | 48.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-32371-v30.xml emd-32371.xml | 16.6 KB 16.6 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_32371.png | 58.7 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-32371 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32371 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_32371_validation.pdf.gz | 520.5 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_32371_full_validation.pdf.gz | 520.1 KB | 表示 | |
XML形式データ | emd_32371_validation.xml.gz | 6.2 KB | 表示 | |
CIF形式データ | emd_32371_validation.cif.gz | 7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32371 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32371 | HTTPS FTP |
-関連構造データ
-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_32371.map.gz / 形式: CCP4 / 大きさ: 52.7 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: 1.091 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
-試料の構成要素
+全体 : Human voltage-gated sodium channel Nav1.7 in complex with auxilia...
+超分子 #1: Human voltage-gated sodium channel Nav1.7 in complex with auxilia...
+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: [(3aS,4R,10aS)-2,6-diamino-10,10-dihydroxy-3a,4,9,10-tetrahydro-3...
+分子 #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
+分子 #7: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phospho...
+分子 #8: CHOLESTEROL HEMISUCCINATE
+分子 #9: 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+分子 #10: (2S,3R,4E)-2-(acetylamino)-3-hydroxyoctadec-4-en-1-yl dihydrogen ...
+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: 7.4 |
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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 K3 (6k x 4k) / 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): 1.8 µm / 最小 デフォーカス(公称値): 1.5 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: EMDB MAP EMDB ID: |
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最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 194430 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |