+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-31494 | |||||||||||||||||||||||||||||||||
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タイトル | Cryo-EM structure of the cholecystokinin receptor CCKBR in complex with gastrin-17 and Gq | |||||||||||||||||||||||||||||||||
マップデータ | CCKBR-Gq complex | |||||||||||||||||||||||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 gastrin receptor activity / type B gastrin/cholecystokinin receptor binding / gland development / gastric acid secretion / cholecystokinin receptor activity / cholecystokinin signaling pathway / pH reduction / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / PLC beta mediated events ...gastrin receptor activity / type B gastrin/cholecystokinin receptor binding / gland development / gastric acid secretion / cholecystokinin receptor activity / cholecystokinin signaling pathway / pH reduction / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / entrainment of circadian clock / regulation of platelet activation / phototransduction, visible light / 1-phosphatidylinositol-3-kinase regulator activity / Gastrin-CREB signalling pathway via PKC and MAPK / digestive tract development / glutamate receptor signaling pathway / : / regulation of canonical Wnt signaling pathway / action potential / peptide hormone binding / photoreceptor outer segment / GTPase activator activity / Peptide ligand-binding receptors / G protein-coupled receptor binding / negative regulation of protein kinase activity / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / blood coagulation / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / nuclear membrane / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / cell surface receptor signaling pathway / protein stabilization / G protein-coupled receptor signaling pathway / lysosomal membrane / intracellular membrane-bounded organelle / GTPase activity / positive regulation of cell population proliferation / synapse / protein-containing complex binding / GTP binding / Golgi apparatus / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol 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: 3.1 Å | |||||||||||||||||||||||||||||||||
データ登録者 | Zhang X / He C / Wang M / Zhou Q / Yang D / Zhu Y / Wu B / Zhao Q | |||||||||||||||||||||||||||||||||
資金援助 | 中国, 10件
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引用 | ジャーナル: Nat Chem Biol / 年: 2021 タイトル: Structures of the human cholecystokinin receptors bound to agonists and antagonists. 著者: Xuefeng Zhang / Chenglin He / Mu Wang / Qingtong Zhou / Dehua Yang / Ya Zhu / Wenbo Feng / Hui Zhang / Antao Dai / Xiaojing Chu / Jia Wang / Zhenlin Yang / Yi Jiang / Ulrich Sensfuss / ...著者: Xuefeng Zhang / Chenglin He / Mu Wang / Qingtong Zhou / Dehua Yang / Ya Zhu / Wenbo Feng / Hui Zhang / Antao Dai / Xiaojing Chu / Jia Wang / Zhenlin Yang / Yi Jiang / Ulrich Sensfuss / Qiuxiang Tan / Shuo Han / Steffen Reedtz-Runge / H Eric Xu / Suwen Zhao / Ming-Wei Wang / Beili Wu / Qiang Zhao / 要旨: Cholecystokinin receptors, CCKR and CCKR, are important neurointestinal peptide hormone receptors and play a vital role in food intake and appetite regulation. Here, we report three crystal ...Cholecystokinin receptors, CCKR and CCKR, are important neurointestinal peptide hormone receptors and play a vital role in food intake and appetite regulation. Here, we report three crystal structures of the human CCKR in complex with different ligands, including one peptide agonist and two small-molecule antagonists, as well as two cryo-electron microscopy structures of CCKR-gastrin in complex with G and G, respectively. These structures reveal the recognition pattern of different ligand types and the molecular basis of peptide selectivity in the cholecystokinin receptor family. By comparing receptor structures in different conformational states, a stepwise activation process of cholecystokinin receptors is proposed. Combined with pharmacological data, our results provide atomic details for differential ligand recognition and receptor activation mechanisms. These insights will facilitate the discovery of potential therapeutics targeting cholecystokinin receptors. | |||||||||||||||||||||||||||||||||
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 | 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_31494.map.gz | 5.4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-31494-v30.xml emd-31494.xml | 20.8 KB 20.8 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_31494.png | 116.3 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-31494 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31494 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「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_31494.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | CCKBR-Gq complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.045 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
+全体 : Cholecystokinin recetor CCKBR in complex with gastrin-17 and Gq
+超分子 #1: Cholecystokinin recetor CCKBR in complex with gastrin-17 and Gq
+超分子 #2: Guanine nucleotide-binding protein G subunits
+超分子 #3: scFv16
+超分子 #4: Gastrin-17
+超分子 #5: cholecystokinin type B receptor
+分子 #1: Guanine nucleotide-binding protein G(q) subunit alpha
+分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #4: scFv16
+分子 #5: Gastrin-17
+分子 #6: Gastrin/cholecystokinin type B receptor
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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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: 7.5 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 1.75 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: SPOT SCAN / 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
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 354647 |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |