登録情報 データベース : EMDB / ID : EMD-35297 ダウンロードとリンクタイトル Structural insights into human brain gut peptide cholecystokinin receptors マップデータ 詳細 試料複合体 : human brain gut peptide cholecystokinin receptors複合体 : cholecystokinin receptorタンパク質・ペプチド : Gastrin/cholecystokinin type B receptor複合体 : G subunit q (Gi1-Gq chimeric)タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2タンパク質・ペプチド : Guanine nucleotide-binding protein G(q) subunit alpha複合体 : scfv16複合体 : CCK-8 詳細 キーワード brain gut peptide receptor Class A G-protein-coupled receptor / NEUROPEPTIDE機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
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 Gastrin receptor / Cholecystokinin receptor / G-protein alpha subunit, group Q / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. ... Gastrin receptor / Cholecystokinin receptor / G-protein alpha subunit, group Q / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / GGL domain / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Gastrin/cholecystokinin type B receptor / Guanine nucleotide-binding protein G(q) subunit alpha / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 類似検索 - 構成要素生物種 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 詳細 データ登録者Ding Y / Zhang H / Liao Y / Chen L / Ji S 資金援助 中国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Natural Science Foundation of China (NSFC) 中国
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 登録 2023年2月8日 - 置き換え 2023年12月6日 ID : EMD-33362 ヘッダ(付随情報) 公開 2023年12月6日 - マップ公開 2023年12月6日 - 更新 2023年12月6日 - 現状 2023年12月6日 処理サイト : PDBj / 状態 : 公開
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