+
データを開く
-
基本情報
登録情報 | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Structure of a human EMC:human Cav1.2 channel complex in GDN detergent (ECAB Map 3) | |||||||||
![]() | Structure of a human EMC:human Cav1.2 channel complex in GDN detergent (ECAB Map 3) | |||||||||
![]() |
| |||||||||
![]() | endoplasmic reticulum membrane protein complex / voltage-gated calcium channel / holdase / biogenesis / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() extrinsic component of endoplasmic reticulum membrane / inorganic cation transmembrane transporter activity / EMC complex / positive regulation of high voltage-gated calcium channel activity / omegasome membrane / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / voltage-gated calcium channel activity involved in AV node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / immune system development / magnesium ion transport ...extrinsic component of endoplasmic reticulum membrane / inorganic cation transmembrane transporter activity / EMC complex / positive regulation of high voltage-gated calcium channel activity / omegasome membrane / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / voltage-gated calcium channel activity involved in AV node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / immune system development / magnesium ion transport / positive regulation of adenylate cyclase activity / membrane depolarization during atrial cardiac muscle cell action potential / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / tail-anchored membrane protein insertion into ER membrane / Miscellaneous transport and binding events / cobalt ion transmembrane transporter activity / ferrous iron transmembrane transporter activity / membrane depolarization during AV node cell action potential / high voltage-gated calcium channel activity / copper ion transport / cardiac conduction / L-type voltage-gated calcium channel complex / magnesium ion transmembrane transporter activity / membrane depolarization during cardiac muscle cell action potential / positive regulation of muscle contraction / cell communication by electrical coupling involved in cardiac conduction / regulation of ventricular cardiac muscle cell action potential / NCAM1 interactions / cardiac muscle cell action potential involved in contraction / camera-type eye development / embryonic forelimb morphogenesis / calcium ion transport into cytosol / voltage-gated calcium channel complex / Phase 0 - rapid depolarisation / alpha-actinin binding / regulation of heart rate by cardiac conduction / calcium ion import across plasma membrane / autophagosome assembly / RHOA GTPase cycle / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / voltage-gated calcium channel activity / positive regulation of endothelial cell proliferation / positive regulation of endothelial cell migration / calcium channel regulator activity / Regulation of insulin secretion / postsynaptic density membrane / calcium ion transmembrane transport / Z disc / positive regulation of angiogenesis / Adrenaline,noradrenaline inhibits insulin secretion / heart development / positive regulation of cytosolic calcium ion concentration / carbohydrate binding / early endosome membrane / angiogenesis / perikaryon / calmodulin binding / early endosome / postsynaptic density / cilium / Golgi membrane / apoptotic process / dendrite / endoplasmic reticulum membrane / endoplasmic reticulum / Golgi apparatus / protein-containing complex / extracellular region / nucleoplasm / metal ion binding / membrane / plasma membrane / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.4 Å | |||||||||
![]() | Chen Z / Mondal A / Abderemane-Ali F / Minor DL | |||||||||
資金援助 | ![]()
| |||||||||
![]() | ![]() タイトル: EMC chaperone-Ca structure reveals an ion channel assembly intermediate. 著者: Zhou Chen / Abhisek Mondal / Fayal Abderemane-Ali / Seil Jang / Sangeeta Niranjan / José L Montaño / Balyn W Zaro / Daniel L Minor / ![]() 要旨: Voltage-gated ion channels (VGICs) comprise multiple structural units, the assembly of which is required for function. Structural understanding of how VGIC subunits assemble and whether chaperone ...Voltage-gated ion channels (VGICs) comprise multiple structural units, the assembly of which is required for function. Structural understanding of how VGIC subunits assemble and whether chaperone proteins are required is lacking. High-voltage-activated calcium channels (Cas) are paradigmatic multisubunit VGICs whose function and trafficking are powerfully shaped by interactions between pore-forming Ca1 or Ca2 Caα (ref. ), and the auxiliary Caβ and Caαδ subunits. Here we present cryo-electron microscopy structures of human brain and cardiac Ca1.2 bound with Caβ to a chaperone-the endoplasmic reticulum membrane protein complex (EMC)-and of the assembled Ca1.2-Caβ-Caαδ-1 channel. These structures provide a view of an EMC-client complex and define EMC sites-the transmembrane (TM) and cytoplasmic (Cyto) docks; interaction between these sites and the client channel causes partial extraction of a pore subunit and splays open the Caαδ-interaction site. The structures identify the Caαδ-binding site for gabapentinoid anti-pain and anti-anxiety drugs, show that EMC and Caαδ interactions with the channel are mutually exclusive, and indicate that EMC-to-Caαδ hand-off involves a divalent ion-dependent step and Ca1.2 element ordering. Disruption of the EMC-Ca complex compromises Ca function, suggesting that the EMC functions as a channel holdase that facilitates channel assembly. Together, the structures reveal a Ca assembly intermediate and EMC client-binding sites that could have wide-ranging implications for the biogenesis of VGICs and other membrane proteins. | |||||||||
履歴 |
|
-
構造の表示
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 | ![]() | 260.4 MB | ![]() | |
---|---|---|---|---|
ヘッダ (付随情報) | ![]() ![]() | 28.1 KB 28.1 KB | 表示 表示 | ![]() |
画像 | ![]() | 132 KB | ||
Filedesc metadata | ![]() | 9.4 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 507.3 KB | 表示 | ![]() |
---|---|---|---|---|
文書・詳細版 | ![]() | 506.8 KB | 表示 | |
XML形式データ | ![]() | 7.8 KB | 表示 | |
CIF形式データ | ![]() | 8.9 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 | ![]() 8eoiMC ![]() 8eogC M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
---|---|
類似構造データ | 類似検索 - 機能・相同性 ![]() |
-
リンク
EMDBのページ | ![]() ![]() |
---|---|
「今月の分子」の関連する項目 |
-
マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Structure of a human EMC:human Cav1.2 channel complex in GDN detergent (ECAB Map 3) | ||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.8466 Å | ||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-
試料の構成要素
+全体 : Ternary complex of the human ER membrane protein complex (EMC) wi...
+超分子 #1: Ternary complex of the human ER membrane protein complex (EMC) wi...
+超分子 #2: Human CaV alpha1C
+超分子 #3: ER membrane protein complex subunit 1
+超分子 #4: Rabbit CaV beta3
+分子 #1: ER membrane protein complex subunit 1
+分子 #2: ER membrane protein complex subunit 2
+分子 #3: ER membrane protein complex subunit 3
+分子 #4: ER membrane protein complex subunit 5
+分子 #5: ER membrane protein complex subunit 6
+分子 #6: ER membrane protein complex subunit 7
+分子 #7: ER membrane protein complex subunit 8
+分子 #8: ER membrane protein complex subunit 10
+分子 #9: Voltage-dependent L-type calcium channel subunit alpha-1C
+分子 #10: Voltage-dependent L-type calcium channel subunit beta-3
+分子 #11: ER membrane protein complex subunit 4
+分子 #13: 2-acetamido-2-deoxy-beta-D-glucopyranose
+分子 #14: (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]sp...
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
![]() | 単粒子再構成法 |
試料の集合状態 | particle |
-
試料調製
濃度 | 1.7 mg/mL |
---|---|
緩衝液 | pH: 8 |
グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV |
-
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 K3 (6k x 4k) / 平均電子線量: 46.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 1.7 µm / 最小 デフォーカス(公称値): 0.9 µm / 倍率(公称値): 105000 |
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: PDB ENTRY PDBモデル - PDB ID: 詳細: 6WW7 (PDB ID) and 7MIY (PDB ID) used to generate the startup model. |
---|---|
最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 487067 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |