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基本情報
登録情報 | データベース: PDB / ID: 7w7f | ||||||
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タイトル | Cryo-EM structure of human NaV1.3/beta1/beta2-ICA121431 | ||||||
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機能・相同性 | ![]() corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / 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 / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / membrane depolarization during Purkinje myocyte cell action potential / regulation of atrial cardiac muscle cell membrane depolarization / cardiac conduction ...corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / 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 / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / membrane depolarization during Purkinje myocyte cell action potential / regulation of atrial cardiac muscle cell membrane depolarization / cardiac conduction / voltage-gated monoatomic ion channel activity / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() 類似検索 - 分子機能 | ||||||
生物種 | ![]() ![]() | ||||||
手法 | ![]() ![]() ![]() | ||||||
![]() | Jiang, D. / Li, X. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis for modulation of human Na1.3 by clinical drug and selective antagonist. 著者: Xiaojing Li / Feng Xu / Hao Xu / Shuli Zhang / Yiwei Gao / Hongwei Zhang / Yanli Dong / Yanchun Zheng / Bei Yang / Jianyuan Sun / Xuejun Cai Zhang / Yan Zhao / Daohua Jiang / ![]() ![]() 要旨: Voltage-gated sodium (Na) channels play fundamental roles in initiating and propagating action potentials. Na1.3 is involved in numerous physiological processes including neuronal development, ...Voltage-gated sodium (Na) channels play fundamental roles in initiating and propagating action potentials. Na1.3 is involved in numerous physiological processes including neuronal development, hormone secretion and pain perception. Here we report structures of human Na1.3/β1/β2 in complex with clinically-used drug bulleyaconitine A and selective antagonist ICA121431. Bulleyaconitine A is located around domain I-II fenestration, providing the detailed view of the site-2 neurotoxin binding site. It partially blocks ion path and expands the pore-lining helices, elucidating how the bulleyaconitine A reduces peak amplitude but improves channel open probability. In contrast, ICA121431 preferentially binds to activated domain IV voltage-sensor, consequently strengthens the Ile-Phe-Met motif binding to its receptor site, stabilizes the channel in inactivated state, revealing an allosterically inhibitory mechanism of Na channels. Our results provide structural details of distinct small-molecular modulators binding sites, elucidate molecular mechanisms of their action on Na channels and pave a way for subtype-selective therapeutic development. | ||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 303.4 KB | 表示 | ![]() |
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PDB形式 | ![]() | 237.7 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 32343MC ![]() 7w77C M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
-Sodium channel subunit beta- ... , 2種, 2分子 BC
#1: 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) ![]() ![]() ![]() ![]() |
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#2: 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) ![]() ![]() ![]() ![]() |
-タンパク質 , 1種, 1分子 D
#3: タンパク質 | ![]() 分子量: 226516.453 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() |
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-糖 , 3種, 7分子 ![](data/chem/img/NAG.gif)
#4: 多糖 | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose![]() |
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#5: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose![]() |
#6: 糖 | ChemComp-NAG / ![]() |
-非ポリマー , 3種, 19分子 ![](data/chem/img/6OU.gif)
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#7: 化合物 | ChemComp-6OU / [( #8: 化合物 | ChemComp-8DE / | #9: 化合物 | ChemComp-9Z9 / ( | |
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-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: ![]() |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: ![]() |
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試料調製
構成要素 | 名称: Sodium channel complex of type 3 subunit alpha with auxiliary beta-1 and beta-2 タイプ: COMPLEX / Entity ID: #1-#3 / 由来: RECOMBINANT |
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由来(天然) | 生物種: ![]() ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色![]() ![]() |
急速凍結![]() | 凍結剤: ETHANE |
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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![]() ![]() |
電子レンズ | モード: BRIGHT FIELD![]() |
撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19_4092: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正![]() | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成![]() | 解像度: 3.35 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 1088844 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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