登録情報 データベース : EMDB / ID : EMD-47300 ダウンロードとリンクタイトル Asenapine-bound serotonin 1A (5-HT1A) receptor-Goa protein complex マップデータ 詳細 試料複合体 : Serotonin 1A (5-HT1A) receptor-Goa protein complex複合体 : Goa proteinタンパク質・ペプチド : Guanine nucleotide-binding protein G(o) subunit alpha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複合体 : Serotonin 1A (5-HT1A) receptor chimeraタンパク質・ペプチド : Soluble cytochrome b562,5-hydroxytryptamine receptor 1Aリガンド : (3aS,12bR)-asenapineリガンド : CHOLESTEROLリガンド : [(2R)-1-[oxidanyl-[(2R,3R,5S,6R)-2,3,5,6-tetrakis(oxidanyl)-4-phosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-3-tetradecanoyloxy-propan-2-yl] (5E,8E)-hexadeca-5,8,11,14-tetraenoate 詳細 キーワード GPCR Signaling Complex / Serotonin Receptor / SIGNALING PROTEIN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
regulation of serotonin secretion / Gi/o-coupled serotonin receptor activity / regulation of hormone secretion / regulation of behavior / receptor-receptor interaction / Serotonin receptors / serotonin receptor activity / G protein-coupled serotonin receptor activity / regulation of dopamine metabolic process / serotonin receptor signaling pathway ... regulation of serotonin secretion / Gi/o-coupled serotonin receptor activity / regulation of hormone secretion / regulation of behavior / receptor-receptor interaction / Serotonin receptors / serotonin receptor activity / G protein-coupled serotonin receptor activity / regulation of dopamine metabolic process / serotonin receptor signaling pathway / neurotransmitter receptor activity / mu-type opioid receptor binding / serotonin metabolic process / corticotropin-releasing hormone receptor 1 binding / serotonin binding / vesicle docking involved in exocytosis / G protein-coupled dopamine receptor signaling pathway / gamma-aminobutyric acid signaling pathway / regulation of heart contraction / parallel fiber to Purkinje cell synapse / exploration behavior / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / regulation of vasoconstriction / behavioral fear response / postsynaptic modulation of chemical synaptic transmission / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / muscle contraction / locomotory behavior / negative regulation of insulin secretion / electron transport chain / GABA-ergic synapse / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / 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 / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADP signalling through P2Y purinoceptor 1 / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / G protein activity / cell body / presynaptic membrane / GTPase binding / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / chemical synaptic transmission / 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 / G alpha (q) signalling events / Ras protein signal transduction / postsynaptic membrane / periplasmic space / electron transfer activity / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / iron ion binding / lysosomal membrane / GTPase activity / positive regulation of cell population proliferation / heme binding / dendrite 類似検索 - 分子機能 5-Hydroxytryptamine 1A receptor / 5-hydroxytryptamine receptor family / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit ... 5-Hydroxytryptamine 1A receptor / 5-hydroxytryptamine receptor family / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / G protein beta WD-40 repeat protein / 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. / 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 5-hydroxytryptamine receptor 1A / Guanine nucleotide-binding protein G(o) subunit alpha / Soluble cytochrome b562 / 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) / Escherichia coli (大腸菌)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.96 Å 詳細 データ登録者Warren AL / Zilberg G / Wacker D 資金援助 米国, 3件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) GM 133504 米国 Other private McKnight Foundation Other private Irma T. Hirschl/Monique Weill-Caulier Trust
引用ジャーナル : Sci Adv / 年 : 2025タイトル : Structural determinants of G protein subtype selectivity at the serotonin receptor 5-HT1A.著者 : Audrey L Warren / Gregory Zilberg / Anwar Abbassi / Alejandro Abraham / Shifan Yang / Daniel Wacker / 要旨 : Activation of the serotonin receptor 5-HT1A has been shown to regulate mood and cognition, making 5-HT1A an important target in the treatment of anxiety, depression, and psychosis. Although the ... Activation of the serotonin receptor 5-HT1A has been shown to regulate mood and cognition, making 5-HT1A an important target in the treatment of anxiety, depression, and psychosis. Although the receptor signals through inhibitory G proteins, more work is necessary to understand differences in transducer coupling and its relation to functional activity. To develop a molecular understanding of the differences underlying transducer coupling and activation, we performed structure-activity relationship studies of 5-HT1A with distinct G proteins. Through a combination of in vitro assays, we identified a potent partial agonist that selectively engages a G protein subtype. We further investigated the differences in G protein engagement at 5-HT1A with cryo-electron microscopy, determining structures of 5-HT1A bound to distinct ligands and G protein subtypes. Combined with subsequent structure-guided mutagenesis and signaling assays, our studies uncover both orthosteric and allosteric determinants of agonist-specific stimulation of distinct transducers. 履歴 登録 2024年10月14日 - ヘッダ(付随情報) 公開 2025年8月13日 - マップ公開 2025年8月13日 - 更新 2025年8月13日 - 現状 2025年8月13日 処理サイト : RCSB / 状態 : 公開
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