登録情報 データベース : PDB / ID : 7t96 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of S2 state ACh-bound M2R-Go signaling complex with a PAM 要素(Guanine nucleotide-binding protein ...) x 3 Muscarinic acetylcholine receptor M2 scFV16 詳細キーワード MEMBRANE PROTEIN / GPCR / signaling complex / muscarinic receptor / acetylcholine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
Muscarinic acetylcholine receptors / symmetric synapse / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / G protein-coupled acetylcholine receptor activity / cholinergic synapse / regulation of smooth muscle contraction / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / G protein-coupled serotonin receptor activity ... Muscarinic acetylcholine receptors / symmetric synapse / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / G protein-coupled acetylcholine receptor activity / cholinergic synapse / regulation of smooth muscle contraction / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / G protein-coupled serotonin receptor activity / arrestin family protein binding / vesicle docking involved in exocytosis / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / asymmetric synapse / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / muscle contraction / axon terminus / presynaptic modulation of chemical synaptic transmission / clathrin-coated endocytic vesicle membrane / locomotory behavior / response to virus / 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-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 / Cargo recognition for clathrin-mediated endocytosis / 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 / Clathrin-mediated endocytosis / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / nervous system development / presynaptic membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / cell body / fibroblast proliferation / G alpha (s) signalling events / Ras protein signal transduction / G alpha (q) signalling events / chemical synaptic transmission / postsynaptic membrane / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / neuronal cell body / glutamatergic synapse / synapse / dendrite / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 Muscarinic acetylcholine receptor M2 / Muscarinic acetylcholine receptor family / 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 ... Muscarinic acetylcholine receptor M2 / Muscarinic acetylcholine receptor family / 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 Chem-2CU / ACETYLCHOLINE / Muscarinic acetylcholine receptor M2 / Guanine nucleotide-binding protein G(o) 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 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.22 Å 詳細データ登録者 Xu, J. / Wang, Q. / Du, Y. / Kobilka, B.K. 資金援助 1件 詳細 詳細を隠す 引用ジャーナル : Nat Commun / 年 : 2023タイトル : Structural and dynamic insights into supra-physiological activation and allosteric modulation of a muscarinic acetylcholine receptor.著者 : Jun Xu / Qinggong Wang / Harald Hübner / Yunfei Hu / Xiaogang Niu / Haoqing Wang / Shoji Maeda / Asuka Inoue / Yuyong Tao / Peter Gmeiner / Yang Du / Changwen Jin / Brian K Kobilka / 要旨 : The M2 muscarinic receptor (M2R) is a prototypical G-protein-coupled receptor (GPCR) that serves as a model system for understanding GPCR regulation by both orthosteric and allosteric ligands. Here, ... The M2 muscarinic receptor (M2R) is a prototypical G-protein-coupled receptor (GPCR) that serves as a model system for understanding GPCR regulation by both orthosteric and allosteric ligands. Here, we investigate the mechanisms governing M2R signaling versatility using cryo-electron microscopy (cryo-EM) and NMR spectroscopy, focusing on the physiological agonist acetylcholine and a supra-physiological agonist iperoxo, as well as a positive allosteric modulator LY2119620. These studies reveal that acetylcholine stabilizes a more heterogeneous M2R-G-protein complex than iperoxo, where two conformers with distinctive G-protein orientations were determined. We find that LY2119620 increases the affinity for both agonists, but differentially modulates agonists efficacy in G-protein and β-arrestin pathways. Structural and spectroscopic analysis suggest that LY211620 stabilizes distinct intracellular conformational ensembles from agonist-bound M2R, which may enhance β-arrestin recruitment while impairing G-protein activation. These results highlight the role of conformational dynamics in the complex signaling behavior of GPCRs, and could facilitate design of better drugs. 履歴 登録 2021年12月18日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2023年1月25日 Provider : repository / タイプ : Initial release改定 1.1 2024年2月7日 Group : Data collection / Database referencesカテゴリ : chem_comp_atom / chem_comp_bond ... chem_comp_atom / chem_comp_bond / citation / citation_author Item : _citation.country / _citation.journal_abbrev ... _citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
すべて表示 表示を減らす