+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6j8i | ||||||||||||||||||
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タイトル | Structure of human voltage-gated sodium channel Nav1.7 in complex with auxiliary beta subunits, ProTx-II and tetrodotoxin (Y1755 up) | ||||||||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / voltage-gated sodium channel (ナトリウムチャネル) | ||||||||||||||||||
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 / membrane depolarization during Purkinje myocyte cell action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of sodium ion transmembrane transporter activity / 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 / membrane depolarization during Purkinje myocyte cell action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / regulation of atrial cardiac muscle cell membrane depolarization / cardiac conduction / voltage-gated sodium channel complex / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / ランヴィエの絞輪 / cardiac muscle cell action potential involved in contraction / high voltage-gated calcium channel activity / locomotion / voltage-gated sodium channel activity / regulation of ventricular cardiac muscle cell membrane repolarization / sodium channel inhibitor activity / neuronal action potential propagation / Interaction between L1 and Ankyrins / sodium ion transport / behavioral response to pain / voltage-gated calcium channel complex / regulation of heart rate by cardiac conduction / Phase 0 - rapid depolarisation / detection of temperature stimulus involved in sensory perception of pain / calcium ion import across plasma membrane / 脱分極 / sodium ion transmembrane transport / sodium channel regulator activity / 介在板 / sensory perception of pain / cardiac muscle contraction / 横行小管 / post-embryonic development / 軸索誘導 / positive regulation of neuron projection development / Sensory perception of sweet, bitter, and umami (glutamate) taste / response to toxic substance / 概日リズム / 遺伝子発現 / nervous system development / response to heat / perikaryon / chemical synaptic transmission / transmembrane transporter binding / 細胞接着 / 炎症 / 神経繊維 / シナプス / extracellular region / 細胞膜 類似検索 - 分子機能 | ||||||||||||||||||
生物種 | Homo sapiens (ヒト) | ||||||||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.2 Å | ||||||||||||||||||
データ登録者 | Shen, H. / Liu, D. / Lei, J. / Yan, N. | ||||||||||||||||||
資金援助 | 中国, 5件
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引用 | ジャーナル: Science / 年: 2019 タイトル: Structures of human Na1.7 channel in complex with auxiliary subunits and animal toxins. 著者: Huaizong Shen / Dongliang Liu / Kun Wu / Jianlin Lei / Nieng Yan / 要旨: Voltage-gated sodium channel Na1.7 represents a promising target for pain relief. Here we report the cryo-electron microscopy structures of the human Na1.7-β1-β2 complex bound to two combinations ...Voltage-gated sodium channel Na1.7 represents a promising target for pain relief. Here we report the cryo-electron microscopy structures of the human Na1.7-β1-β2 complex bound to two combinations of pore blockers and gating modifier toxins (GMTs), tetrodotoxin with protoxin-II and saxitoxin with huwentoxin-IV, both determined at overall resolutions of 3.2 angstroms. The two structures are nearly identical except for minor shifts of voltage-sensing domain II (VSD), whose S3-S4 linker accommodates the two GMTs in a similar manner. One additional protoxin-II sits on top of the S3-S4 linker in VSD The structures may represent an inactivated state with all four VSDs "up" and the intracellular gate closed. The structures illuminate the path toward mechanistic understanding of the function and disease of Na1.7 and establish the foundation for structure-aided development of analgesics. | ||||||||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6j8i.cif.gz | 320.4 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6j8i.ent.gz | 243.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6j8i.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/j8/6j8i ftp://data.pdbj.org/pub/pdb/validation_reports/j8/6j8i | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-Sodium channel subunit beta- ... , 2種, 2分子 CB
#1: タンパク質 | 分子量: 24355.859 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: SCN2B, UNQ326/PRO386 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: O60939 |
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#3: タンパク質 | 分子量: 24732.115 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: SCN1B / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q07699 |
-タンパク質 / 非ポリマー , 2種, 2分子 A
#2: タンパク質 | 分子量: 231211.922 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: SCN9A, NENA / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q15858 |
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#6: 化合物 | ChemComp-9SR / ( |
-糖 , 2種, 9分子
#4: 多糖 | #5: 糖 | ChemComp-NAG / |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Complex of human voltage-gated sodium channel Nav1.7 with auxiliary beta subunits, ProTx-II and tetrodotoxin タイプ: COMPLEX / Entity ID: #1-#3 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy |
撮影 | 電子線照射量: 48 e/Å2 フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.11.1_2575: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア | 名称: RELION / バージョン: 2.1 / カテゴリ: 分類 | ||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 263205 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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