+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-30446 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | human KCNQ2-CaM in apo state | |||||||||
マップデータ | ||||||||||
試料 |
| |||||||||
キーワード | ion channel / TRANSPORT PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 axon initial segment / Voltage gated Potassium channels / node of Ranvier / Interaction between L1 and Ankyrins / ankyrin binding / negative regulation of high voltage-gated calcium channel activity / positive regulation of cyclic-nucleotide phosphodiesterase activity / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / positive regulation of ryanodine-sensitive calcium-release channel activity ...axon initial segment / Voltage gated Potassium channels / node of Ranvier / Interaction between L1 and Ankyrins / ankyrin binding / negative regulation of high voltage-gated calcium channel activity / positive regulation of cyclic-nucleotide phosphodiesterase activity / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / negative regulation of peptidyl-threonine phosphorylation / negative regulation of ryanodine-sensitive calcium-release channel activity / protein phosphatase activator activity / voltage-gated potassium channel activity / action potential / : / adenylate cyclase binding / catalytic complex / detection of calcium ion / regulation of cardiac muscle contraction / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / : / titin binding / regulation of calcium-mediated signaling / positive regulation of protein autophosphorylation / voltage-gated potassium channel complex / sperm midpiece / potassium ion transmembrane transport / calcium channel complex / substantia nigra development / adenylate cyclase activator activity / regulation of heart rate / sarcomere / protein serine/threonine kinase activator activity / regulation of cytokinesis / positive regulation of peptidyl-threonine phosphorylation / spindle microtubule / response to calcium ion / positive regulation of protein serine/threonine kinase activity / G2/M transition of mitotic cell cycle / spindle pole / calcium-dependent protein binding / myelin sheath / nervous system development / chemical synaptic transmission / vesicle / transmembrane transporter binding / calmodulin binding / G protein-coupled receptor signaling pathway / centrosome / synapse / calcium ion binding / protein kinase binding / protein-containing complex / membrane / nucleus / plasma membrane / cytoplasm 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: 3.6 Å | |||||||||
データ登録者 | Li X / Lv D | |||||||||
資金援助 | 中国, 2件
| |||||||||
引用 | ジャーナル: Cell Res / 年: 2021 タイトル: Molecular basis for ligand activation of the human KCNQ2 channel. 著者: Xiaoxiao Li / Qiansen Zhang / Peipei Guo / Jie Fu / Lianghe Mei / Dashuai Lv / Jiangqin Wang / Dongwu Lai / Sheng Ye / Huaiyu Yang / Jiangtao Guo / 要旨: The voltage-gated potassium channel KCNQ2 is responsible for M-current in neurons and is an important drug target to treat epilepsy, pain and several other diseases related to neuronal hyper- ...The voltage-gated potassium channel KCNQ2 is responsible for M-current in neurons and is an important drug target to treat epilepsy, pain and several other diseases related to neuronal hyper-excitability. A list of synthetic compounds have been developed to directly activate KCNQ2, yet our knowledge of their activation mechanism is limited, due to lack of high-resolution structures. Here, we report cryo-electron microscopy (cryo-EM) structures of the human KCNQ2 determined in apo state and in complex with two activators, ztz240 or retigabine, which activate KCNQ2 through different mechanisms. The activator-bound structures, along with electrophysiology analysis, reveal that ztz240 binds at the voltage-sensing domain and directly stabilizes it at the activated state, whereas retigabine binds at the pore domain and activates the channel by an allosteric modulation. By accurately defining ligand-binding sites, these KCNQ2 structures not only reveal different ligand recognition and activation mechanisms, but also provide a structural basis for drug optimization and design. | |||||||||
履歴 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_30446.map.gz | 47.4 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-30446-v30.xml emd-30446.xml | 11.5 KB 11.5 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_30446.png | 174.9 KB | ||
Filedesc metadata | emd-30446.cif.gz | 5.5 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-30446 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30446 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_30446_validation.pdf.gz | 519 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_30446_full_validation.pdf.gz | 518.5 KB | 表示 | |
XML形式データ | emd_30446_validation.xml.gz | 5.9 KB | 表示 | |
CIF形式データ | emd_30446_validation.cif.gz | 6.8 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30446 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30446 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「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_30446.map.gz / 形式: CCP4 / 大きさ: 52.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ボクセルのサイズ | X=Y=Z: 1.014 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
|
-添付データ
-試料の構成要素
-全体 : voltage-gated potassium channel KCNQ2
全体 | 名称: voltage-gated potassium channel KCNQ2 |
---|---|
要素 |
|
-超分子 #1: voltage-gated potassium channel KCNQ2
超分子 | 名称: voltage-gated potassium channel KCNQ2 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
---|
-超分子 #2: Potassium voltage-gated channel subfamily KQT member 2
超分子 | 名称: Potassium voltage-gated channel subfamily KQT member 2 タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1 |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
-超分子 #3: Calmodulin-3
超分子 | 名称: Calmodulin-3 / タイプ: complex / ID: 3 / 親要素: 1 / 含まれる分子: #2 |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Potassium voltage-gated channel subfamily KQT member 2
分子 | 名称: Potassium voltage-gated channel subfamily KQT member 2 タイプ: protein_or_peptide / ID: 1 / コピー数: 4 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 73.627812 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MAGKPPKRNA FYRKLQNFLY NVLERPRGWA FIYHAYVFLL VFSCLVLSVF STIKEYEKSS EGALYILEIV TIVVFGVEYF VRIWAAGCC CRYRGWRGRL KFARKPFCVI DIMVLIASIA VLAAGSQGNV FATSALRSLR FLQILRMIRM DRRGGTWKLL G SVVYAHSK ...文字列: MAGKPPKRNA FYRKLQNFLY NVLERPRGWA FIYHAYVFLL VFSCLVLSVF STIKEYEKSS EGALYILEIV TIVVFGVEYF VRIWAAGCC CRYRGWRGRL KFARKPFCVI DIMVLIASIA VLAAGSQGNV FATSALRSLR FLQILRMIRM DRRGGTWKLL G SVVYAHSK ELVTAWYIGF LCLILASFLV YLAEKGENDH FDTYADALWW GLITLTTIGY GDKYPQTWNG RLLAATFTLI GV SFFALPA GILGSGFALK VQEQHRQKHF EKRRNPAAGL IQSAWRFYAT NLSRTDLHST WQYYERTVTV PMYSSQTQTY GAS RLIPPL NQLELLRNLK SKSGLAFRKD PPPEPSPSKG SPCRGPLCGC CPGRSSQKVS LKDRVFSSPR GVAAKGKGSP QAQT VRRSP SADQSLEDSP SKVPKSWSFG DRSRARQAFR IKGAASRQNS EEASLPGEDI VDDKSCPCEF VTEDLTPGLK VSIRA VCVM RFLVSKRKFK ESLRPYDVMD VIEQYSAGHL DMLSRIKSLQ SRVDQIVGRG PAITDKDRTK GPAEAELPED PSMMGR LGK VEKQVLSMEK KLDFLVNIYM QRMGIPPTET EAYFGAKEPE PAPPYHSPED SREHVDRHGC IVKIVRSSSS TGQKNFS VE GGSSGGWSHP QFEK UniProtKB: Potassium voltage-gated channel subfamily KQT member 2 |
-分子 #2: Calmodulin-3
分子 | 名称: Calmodulin-3 / タイプ: protein_or_peptide / ID: 2 / コピー数: 4 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 16.852545 KDa |
配列 | 文字列: MADQLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ DMINEVDADG NGTIDFPEFL TMMARKMKDT DSEEEIREA FRVFDKDGNG YISAAELRHV MTNLGEKLTD EEVDEMIREA DIDGDGQVNY EEFVQMMTAK UniProtKB: Calmodulin-3 |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
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: 8 |
---|---|
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 1.556 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 |
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: NONE |
---|---|
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 78605 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: PROJECTION MATCHING |