登録情報 データベース : EMDB / ID : EMD-33247 ダウンロードとリンクタイトル Cryo-EM structure of the Neuromedin U receptor 2 (NMUR2) in complex with G Protein and its endogeneous Peptide-Agonist NMU25 マップデータ 詳細 試料複合体 : NmU25-NMU2-Gi1 complexタンパク質・ペプチド : Neuromedin-U-25タンパク質・ペプチド : Neuromedin-U receptor 2タンパク質・ペプチド : Guanine nucleotide-binding protein G(i) subunit alpha-1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 詳細機能・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
neuromedin U receptor activity / neuromedin U binding / type 1 neuromedin U receptor binding / type 2 neuromedin U receptor binding / neuromedin U receptor binding / : / reduction of food intake in response to dietary excess / neuropeptide receptor activity / intracellularly calcium-gated chloride channel activity / regulation of feeding behavior ... neuromedin U receptor activity / neuromedin U binding / type 1 neuromedin U receptor binding / type 2 neuromedin U receptor binding / neuromedin U receptor binding / : / reduction of food intake in response to dietary excess / neuropeptide receptor activity / intracellularly calcium-gated chloride channel activity / regulation of feeding behavior / regulation of grooming behavior / regulation of smooth muscle contraction / regulation of sensory perception of pain / grooming behavior / positive regulation of smooth muscle contraction / feeding behavior / arachidonic acid secretion / temperature homeostasis / response to pain / Adenylate cyclase inhibitory pathway / neuropeptide signaling pathway / positive regulation of protein localization to cell cortex / positive regulation of synaptic transmission / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / energy homeostasis / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / central nervous system development / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / calcium-mediated signaling / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / terminal bouton / 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 / response to peptide hormone / 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 / calcium ion transport / GPER1 signaling / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / cell-cell signaling / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / cell cortex / midbody / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell cycle / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / signaling receptor binding 類似検索 - 分子機能 Neuromedin U receptor / Neuromedin U receptor, type 2 / Neuromedin-U receptor 2, C-terminal domain / Neuromedin-U receptor 2, C-terminal / Neuromedin U, C-terminal / Neuromedin-U / Neuromedin U / Neuromedin U / Neuromedin U, amidation site / Neuromedin U signature. ... Neuromedin U receptor / Neuromedin U receptor, type 2 / Neuromedin-U receptor 2, C-terminal domain / Neuromedin-U receptor 2, C-terminal / Neuromedin U, C-terminal / Neuromedin-U / Neuromedin U / Neuromedin U / Neuromedin U, amidation site / Neuromedin U signature. / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / 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 Neuromedin-U / 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 / Guanine nucleotide-binding protein G(i) subunit alpha-1 / Neuromedin-U receptor 2 類似検索 - 構成要素生物種 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 : 3.3 Å 詳細 データ登録者Zhao W / Wenru Z / Mu W / Minmin L / Shutian C / Tingting T / Gisela S / Holger W / Albert B / Cuiying Y ...Zhao W / Wenru Z / Mu W / Minmin L / Shutian C / Tingting T / Gisela S / Holger W / Albert B / Cuiying Y / Xiaojing C / Han S / Wu B / Zhao Q 資金援助 中国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Science Foundation (NSF, China) 31825010 中国
引用ジャーナル : Nat Commun / 年 : 2022タイトル : Ligand recognition and activation of neuromedin U receptor 2.著者 : Wenli Zhao / Wenru Zhang / Mu Wang / Minmin Lu / Shutian Chen / Tingting Tang / Gisela Schnapp / Holger Wagner / Albert Brennauer / Cuiying Yi / Xiaojing Chu / Shuo Han / Beili Wu / Qiang Zhao / 要旨 : Neuromedin U receptor 2 (NMU2), an emerging attractive target for treating obesity, has shown the capability in reducing food intake and regulating energy metabolism when activated. However, drug ... Neuromedin U receptor 2 (NMU2), an emerging attractive target for treating obesity, has shown the capability in reducing food intake and regulating energy metabolism when activated. However, drug development of NMU2 was deferred partially due to the lack of structural information. Here, we present the cryo-electron microscopy (cryo-EM) structure of NMU2 bound to the endogenous agonist NmU-25 and G at 3.3 Å resolution. Combined with functional and computational data, the structure reveals the key factors that govern the recognition and selectivity of peptide agonist as well as non-peptide antagonist, providing the structural basis for design of novel and highly selective drugs targeting NMU2. In addition, a 25-degree rotation of G protein in reference to NMU2 is also observed compared in other structures of class A GPCR-G complexes, suggesting heterogeneity in the processes of G protein-coupled receptors (GPCRs) activation and G protein coupling. 履歴 登録 2022年4月19日 - ヘッダ(付随情報) 公開 2023年2月22日 - マップ公開 2023年2月22日 - 更新 2023年2月22日 - 現状 2023年2月22日 処理サイト : PDBj / 状態 : 公開
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