+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-35297 | ||||||||||||
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タイトル | Structural insights into human brain gut peptide cholecystokinin receptors | ||||||||||||
マップデータ | |||||||||||||
試料 |
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キーワード | brain gut peptide receptor Class A G-protein-coupled receptor / NEUROPEPTIDE | ||||||||||||
機能・相同性 | 機能・相同性情報 gastrin receptor activity / type B gastrin/cholecystokinin receptor binding / gland development / cholecystokinin receptor activity / cholecystokinin signaling pathway / gastric acid secretion / 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 / cholecystokinin receptor activity / cholecystokinin signaling pathway / gastric acid secretion / pH reduction / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / PLC beta mediated events / entrainment of circadian clock / phospholipase C-activating dopamine receptor signaling pathway / regulation of platelet activation / digestive tract development / phototransduction, visible light / 1-phosphatidylinositol-3-kinase regulator activity / Gastrin-CREB signalling pathway via PKC and MAPK / regulation of canonical Wnt signaling pathway / glutamate receptor signaling pathway / action potential / peptide hormone binding / photoreceptor outer segment / GTPase activator activity / G-protein beta/gamma-subunit complex binding / Peptide ligand-binding receptors / G protein-coupled receptor binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / negative regulation of protein kinase activity / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / 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 / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / blood coagulation / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / 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 / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / nuclear membrane / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / 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 / GTP binding / protein-containing complex binding / Golgi apparatus / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) / Mus musculus (ハツカネズミ) | ||||||||||||
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 | Ding Y / Zhang H / Liao Y / Chen L / Ji S | ||||||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Cell Discov / 年: 2022 タイトル: Structural insights into human brain-gut peptide cholecystokinin receptors. 著者: Yu Ding / Huibing Zhang / Yu-Ying Liao / Li-Nan Chen / Su-Yu Ji / Jiao Qin / Chunyou Mao / Dan-Dan Shen / Lin Lin / Hao Wang / Yan Zhang / Xiao-Ming Li / 要旨: The intestinal hormone and neuromodulator cholecystokinin (CCK) receptors CCK1R and CCK2R act as a signaling hub in brain-gut axis, mediating digestion, emotion, and memory regulation. CCK receptors ...The intestinal hormone and neuromodulator cholecystokinin (CCK) receptors CCK1R and CCK2R act as a signaling hub in brain-gut axis, mediating digestion, emotion, and memory regulation. CCK receptors exhibit distinct preferences for ligands in different posttranslational modification (PTM) states. CCK1R couples to G and G, whereas CCK2R primarily couples to G. Here we report the cryo-electron microscopy (cryo-EM) structures of CCK1R-G signaling complexes liganded either by sulfated cholecystokinin octapeptide (CCK-8) or a CCK1R-selective small-molecule SR146131, and CCK2R-G complexes stabilized by either sulfated CCK-8 or a CCK2R-selective ligand gastrin-17. Our structures reveal a location-conserved yet charge-distinct pocket discriminating the effects of ligand PTM states on receptor subtype preference, the unique pocket topology underlying selectivity of SR146131 and gastrin-17, the conformational changes in receptor activation, and key residues contributing to G protein subtype specificity, providing multiple structural templates for drug design targeting the brain-gut axis. | ||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_35297.map.gz | 24.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-35297-v30.xml emd-35297.xml | 21.6 KB 21.6 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_35297.png | 65.8 KB | ||
Filedesc metadata | emd-35297.cif.gz | 6.8 KB | ||
その他 | emd_35297_half_map_1.map.gz emd_35297_half_map_2.map.gz | 24.1 MB 24.1 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-35297 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35297 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_35297_validation.pdf.gz | 823 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_35297_full_validation.pdf.gz | 822.5 KB | 表示 | |
XML形式データ | emd_35297_validation.xml.gz | 10.5 KB | 表示 | |
CIF形式データ | emd_35297_validation.cif.gz | 12.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35297 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35297 | 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_35297.map.gz / 形式: CCP4 / 大きさ: 27 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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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: 1.014 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #2
ファイル | emd_35297_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_35297_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : human brain gut peptide cholecystokinin receptors
+超分子 #1: human brain gut peptide cholecystokinin receptors
+超分子 #2: cholecystokinin receptor
+超分子 #3: G subunit q (Gi1-Gq chimeric)
+超分子 #4: scfv16
+超分子 #5: CCK-8
+分子 #1: Gastrin/cholecystokinin type B receptor
+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: Guanine nucleotide-binding protein G(q) subunit alpha
+分子 #6: CCK-8
-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 K2 QUANTUM (4k x 4k) 平均電子線量: 62.0 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 / 最大 デフォーカス(公称値): 5.0 µm / 最小 デフォーカス(公称値): 1.2 µm |
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: EMDB MAP EMDB ID: |
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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: 669008 |
初期 角度割当 | タイプ: RANDOM ASSIGNMENT |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |