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基本情報
登録情報 | データベース: PDB / ID: 8t6l | |||||||||||||||
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タイトル | Cryo-EM structure of rat cardiac sodium channel NaV1.5 with batrachotoxin analog BTX-B | |||||||||||||||
![]() | Sodium channel protein type 5 subunit alpha,Green fluorescent protein | |||||||||||||||
![]() | MEMBRANE PROTEIN / Ion channel / Sodium channel / Voltage-gated channel / Sodium transport | |||||||||||||||
機能・相同性 | ![]() voltage-gated sodium channel activity involved in AV node cell action potential / voltage-gated sodium channel activity involved in bundle of His cell action potential / voltage-gated sodium channel activity involved in SA node cell action potential / bundle of His cell action potential / AV node cell action potential / sodium channel complex / SA node cell action potential / AV node cell to bundle of His cell communication / membrane depolarization during SA node cell action potential / response to denervation involved in regulation of muscle adaptation ...voltage-gated sodium channel activity involved in AV node cell action potential / voltage-gated sodium channel activity involved in bundle of His cell action potential / voltage-gated sodium channel activity involved in SA node cell action potential / bundle of His cell action potential / AV node cell action potential / sodium channel complex / SA node cell action potential / AV node cell to bundle of His cell communication / membrane depolarization during SA node cell action potential / response to denervation involved in regulation of muscle adaptation / cardiac ventricle development / regulation of ventricular cardiac muscle cell membrane depolarization / regulation of atrial cardiac muscle cell membrane repolarization / membrane depolarization during atrial cardiac muscle cell action potential / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transport / brainstem development / membrane depolarization during AV node cell action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / membrane depolarization during bundle of His cell action potential / positive regulation of action potential / atrial cardiac muscle cell action potential / membrane depolarization during Purkinje myocyte cell action potential / telencephalon development / regulation of atrial cardiac muscle cell membrane depolarization / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / sodium ion import across plasma membrane / ventricular cardiac muscle cell action potential / cardiac muscle cell action potential involved in contraction / regulation of ventricular cardiac muscle cell membrane repolarization / regulation of cardiac muscle cell contraction / voltage-gated sodium channel complex / membrane depolarization during action potential / voltage-gated sodium channel activity / ankyrin binding / sodium ion transport / positive regulation of heart rate / nitric-oxide synthase binding / fibroblast growth factor binding / regulation of heart rate by cardiac conduction / odontogenesis of dentin-containing tooth / membrane depolarization / intercalated disc / sodium ion transmembrane transport / lateral plasma membrane / neuronal action potential / cardiac muscle contraction / T-tubule / cellular response to calcium ion / regulation of heart rate / bioluminescence / cerebellum development / generation of precursor metabolites and energy / caveola / positive regulation of epithelial cell proliferation / response to organic cyclic compound / sarcolemma / Z disc / scaffold protein binding / transmembrane transporter binding / calmodulin binding / protein domain specific binding / axon / ubiquitin protein ligase binding / protein kinase binding / perinuclear region of cytoplasm / enzyme binding / cell surface / endoplasmic reticulum / membrane / plasma membrane 類似検索 - 分子機能 | |||||||||||||||
生物種 | ![]() ![]() ![]() ![]() | |||||||||||||||
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: 3.3 Å | |||||||||||||||
![]() | Tonggu, L. / Wisedchaisri, G. / Gamal El-Din, T.M. / Zheng, N. / Catterall, W.A. | |||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Dual receptor-sites reveal the structural basis for hyperactivation of sodium channels by poison-dart toxin batrachotoxin. 著者: Lige Tonggu / Goragot Wisedchaisri / Tamer M Gamal El-Din / Michael J Lenaeus / Matthew M Logan / Tatsuya Toma / Justin Du Bois / Ning Zheng / William A Catterall / ![]() ![]() 要旨: The poison dart toxin batrachotoxin is exceptional for its high potency and toxicity, and for its multifaceted modification of the function of voltage-gated sodium channels. By using cryogenic ...The poison dart toxin batrachotoxin is exceptional for its high potency and toxicity, and for its multifaceted modification of the function of voltage-gated sodium channels. By using cryogenic electron microscopy, we identify two homologous, but nonidentical receptor sites that simultaneously bind two molecules of toxin, one at the interface between Domains I and IV, and the other at the interface between Domains III and IV of the cardiac sodium channel. Together, these two bound toxin molecules stabilize α/π helical conformation in the S6 segments that gate the pore, and one of the bound BTX-B molecules interacts with the crucial Lys1421 residue that is essential for sodium conductance and selectivity via an apparent water-bridged hydrogen bond. Overall, our structure provides insight into batrachotoxin's potency, efficacy, and multifaceted functional effects on voltage-gated sodium channels via a dual receptor site mechanism. | |||||||||||||||
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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 | ![]() | 313.2 KB | 表示 | ![]() |
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PDB形式 | ![]() | 234.8 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 2.6 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 2.6 MB | 表示 | |
XML形式データ | ![]() | 54.3 KB | 表示 | |
CIF形式データ | ![]() | 79.3 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 41071MC 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
-タンパク質 , 1種, 1分子 A
#1: タンパク質 | 分子量: 213523.875 Da / 分子数: 1 / 変異: A33T,G214D / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() ![]() ![]() 遺伝子: Scn5a, GFP / 細胞株 (発現宿主): HEK293GnTI- / 発現宿主: ![]() |
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-糖 , 4種, 7分子 ![](data/chem/img/NAG.gif)
#2: 多糖 | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose タイプ: oligosaccharide / 分子量: 748.682 Da / 分子数: 1 / 由来タイプ: 組換発現 | ||||
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#3: 多糖 | #4: 多糖 | alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #5: 糖 | |
-非ポリマー , 5種, 26分子 ![](data/chem/img/LBN.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/9Z9.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/9Z9.gif)
![](data/chem/img/HOH.gif)
#6: 化合物 | ChemComp-LBN / #7: 化合物 | ChemComp-Y01 / #8: 化合物 | #9: 化合物 | 分子量: 521.644 Da / 分子数: 2 / 由来タイプ: 合成 / 式: C31H39NO6 / タイプ: SUBJECT OF INVESTIGATION #10: 水 | ChemComp-HOH / | |
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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: 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 |
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試料調製
構成要素 | 名称: Sodium channel NaV1.5 and batrachotoxinin-A 20-alpha-benzoate タイプ: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / 由来: RECOMBINANT | |||||||||||||||||||||||||
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分子量 | 値: 0.2 MDa / 実験値: NO | |||||||||||||||||||||||||
由来(天然) | 生物種: ![]() ![]() | |||||||||||||||||||||||||
由来(組換発現) | 生物種: ![]() | |||||||||||||||||||||||||
緩衝液 | pH: 6 | |||||||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | |||||||||||||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 295 K |
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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 / 倍率(公称値): 105000 X / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 500 nm / Cs: 2.7 mm / C2レンズ絞り径: 100 µm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 平均露光時間: 2.04 sec. / 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 2 / 実像数: 7542 |
電子光学装置 | エネルギーフィルター名称: GIF Bioquantum / エネルギーフィルタースリット幅: 20 eV |
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解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 1690000 | ||||||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 86763 / アルゴリズム: FOURIER SPACE / クラス平均像の数: 1 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | B value: 49.4 / プロトコル: FLEXIBLE FIT / 空間: REAL / Target criteria: Cross-correlation coefficient | ||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 6UZ0 Accession code: 6UZ0 / Source name: PDB / タイプ: experimental model | ||||||||||||||||||||||||||||||||||||||||
精密化 | 交差検証法: NONE 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 58.27 Å2 | ||||||||||||||||||||||||||||||||||||||||
拘束条件 |
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