+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7phl | ||||||
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タイトル | Human voltage-gated potassium channel Kv3.1 (with EDTA) | ||||||
要素 | Potassium voltage-gated channel, Shaw-related subfamily, member 1 | ||||||
キーワード | TRANSPORT PROTEIN / Channel / potassium channel / tetramer / voltage-gated / membrane protein | ||||||
機能・相同性 | 機能・相同性情報 response to nerve growth factor / globus pallidus development / response to auditory stimulus / response to fibroblast growth factor / response to potassium ion / corpus callosum development / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of potassium ion transmembrane transport / delayed rectifier potassium channel activity / Voltage gated Potassium channels ...response to nerve growth factor / globus pallidus development / response to auditory stimulus / response to fibroblast growth factor / response to potassium ion / corpus callosum development / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of potassium ion transmembrane transport / delayed rectifier potassium channel activity / Voltage gated Potassium channels / response to light intensity / optic nerve development / action potential / neuronal cell body membrane / response to amine / kinesin binding / calyx of Held / voltage-gated potassium channel activity / axolemma / voltage-gated potassium channel complex / axon terminus / dendrite membrane / potassium ion transmembrane transport / cerebellum development / protein tetramerization / potassium ion transport / protein homooligomerization / response to toxic substance / cellular response to xenobiotic stimulus / presynaptic membrane / postsynaptic membrane / transmembrane transporter binding / cell surface / plasma membrane 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 | Chi, G. / Qian, P. / Castro-Hartmann, P. / Venkaya, S. / Singh, N.K. / McKinley, G. / Mukhopadhyay, S.M.M. / Fernandez-Cid, A. / Pike, A.C.W. / Marsden, B. ...Chi, G. / Qian, P. / Castro-Hartmann, P. / Venkaya, S. / Singh, N.K. / McKinley, G. / Mukhopadhyay, S.M.M. / Fernandez-Cid, A. / Pike, A.C.W. / Marsden, B. / MacLean, E.M. / Sader, K. / Burgess-Brown, N.A. / Duerr, K.L. | ||||||
資金援助 | 英国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Cryo-EM structure of the human Kv3.1 channel reveals gating control by the cytoplasmic T1 domain. 著者: Gamma Chi / Qiansheng Liang / Akshay Sridhar / John B Cowgill / Kasim Sader / Mazdak Radjainia / Pu Qian / Pablo Castro-Hartmann / Shayla Venkaya / Nanki Kaur Singh / Gavin McKinley / ...著者: Gamma Chi / Qiansheng Liang / Akshay Sridhar / John B Cowgill / Kasim Sader / Mazdak Radjainia / Pu Qian / Pablo Castro-Hartmann / Shayla Venkaya / Nanki Kaur Singh / Gavin McKinley / Alejandra Fernandez-Cid / Shubhashish M M Mukhopadhyay / Nicola A Burgess-Brown / Lucie Delemotte / Manuel Covarrubias / Katharina L Dürr / 要旨: Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic ...Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic disorders, yet the structural determinants for the unusual gating properties remain elusive. Here, we present cryo-electron microscopy structures of the human Kv3.1a channel, revealing a unique arrangement of the cytoplasmic tetramerization domain T1 which facilitates interactions with C-terminal axonal targeting motif and key components of the gating machinery. Additional interactions between S1/S2 linker and turret domain strengthen the interface between voltage sensor and pore domain. Supported by molecular dynamics simulations, electrophysiological and mutational analyses, we identify several residues in the S4/S5 linker which influence the gating kinetics and an electrostatic interaction between acidic residues in α6 of T1 and R449 in the pore-flanking S6T helices. These findings provide insights into gating control and disease mechanisms and may guide strategies for the design of pharmaceutical drugs targeting Kv3 channels. | ||||||
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 | 7phl.cif.gz | 291.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7phl.ent.gz | 232.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7phl.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
文書・要旨 | 7phl_validation.pdf.gz | 1.5 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7phl_full_validation.pdf.gz | 1.5 MB | 表示 | |
XML形式データ | 7phl_validation.xml.gz | 61.9 KB | 表示 | |
CIF形式データ | 7phl_validation.cif.gz | 87.1 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ph/7phl ftp://data.pdbj.org/pub/pdb/validation_reports/ph/7phl | HTTPS FTP |
-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
#1: タンパク質 | 分子量: 58850.078 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: KCNC1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q3KNS8 #2: 化合物 | ChemComp-PCF / #3: 化合物 | ChemComp-ZN / #4: 化合物 | ChemComp-K / 研究の焦点であるリガンドがあるか | N | |
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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: Homotetrameric complex of human Kv3.1 / タイプ: COMPLEX / Entity ID: #1 / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
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: 7.5 |
試料 | 濃度: 3 mg/ml / 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: TFS 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 FIELD |
撮影 | 電子線照射量: 47.6 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.17.1_3660: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア | 名称: EPU / カテゴリ: 画像取得 | ||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
対称性 | 点対称性: C4 (4回回転対称) | ||||||||||||||||||||||||
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: 217788 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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