登録情報 データベース : EMDB / ID : EMD-27966 ダウンロードとリンクタイトル CryoEM structure of miniGq-coupled hM3Dq in complex with DCZ マップデータCryoEM structure of Gq-coupled hM3Dq in complex with DCZ 詳細 試料複合体 : Gq-coupled hM3R complex複合体 : muscarinic acetylcholine receptor 3, miniGq protein, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2タンパク質・ペプチド : Muscarinic acetylcholine receptor M3タンパク質・ペプチド : miniGq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 : Single-chain variable fragment scFv16リガンド : 11-(4-methylpiperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine 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
regulation of monoatomic ion transmembrane transporter activity / regulation of vascular associated smooth muscle contraction / saliva secretion / ion channel modulating, G protein-coupled receptor signaling pathway / Acetylcholine regulates insulin secretion / Muscarinic acetylcholine receptors / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / G protein-coupled acetylcholine receptor activity / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / positive regulation of smooth muscle contraction ... regulation of monoatomic ion transmembrane transporter activity / regulation of vascular associated smooth muscle contraction / saliva secretion / ion channel modulating, G protein-coupled receptor signaling pathway / Acetylcholine regulates insulin secretion / Muscarinic acetylcholine receptors / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / G protein-coupled acetylcholine receptor activity / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / positive regulation of smooth muscle contraction / phosphatidylinositol phospholipase C activity / G protein-coupled serotonin receptor activity / acetylcholine binding / acetylcholine receptor signaling pathway / ligand-gated ion channel signaling pathway / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / smooth muscle contraction / basal plasma membrane / calcium-mediated signaling / Olfactory Signaling Pathway / Activation of the phototransduction cascade / protein modification process / 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 / positive regulation of insulin secretion / 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 / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / signaling receptor activity / nervous system development / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / chemical synaptic transmission / basolateral plasma membrane / postsynaptic membrane / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / シナプス / 樹状突起 / protein-containing complex binding / endoplasmic reticulum membrane / シグナル伝達 / extracellular exosome / 生体膜 / 細胞膜 / 細胞質基質 / 細胞質 類似検索 - 分子機能 Muscarinic acetylcholine receptor M3 / Muscarinic acetylcholine receptor family / Serpentine type 7TM GPCR chemoreceptor Srsx / 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 ... Muscarinic acetylcholine receptor M3 / Muscarinic acetylcholine receptor family / Serpentine type 7TM GPCR chemoreceptor Srsx / 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リピート / WD40リピート / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily 類似検索 - ドメイン・相同性 Muscarinic acetylcholine receptor M3 / 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 : 2.69 Å 詳細 データ登録者Zhang S / Fay JF / Roth BL 資金援助 米国, 2件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK) U24DK1169195 米国 National Institutes of Health/National Institute of Mental Health (NIH/NIMH) Psychoactive Drug Screening (PDSP) 米国
引用ジャーナル : Nature / 年 : 2022タイトル : Molecular basis for selective activation of DREADD-based chemogenetics.著者 : Shicheng Zhang / Ryan H Gumpper / Xi-Ping Huang / Yongfeng Liu / Brian E Krumm / Can Cao / Jonathan F Fay / Bryan L Roth / 要旨 : Designer receptors exclusively activated by designer drugs (DREADDs) represent a powerful chemogenetic technology for the remote control of neuronal activity and cellular signalling. The muscarinic ... Designer receptors exclusively activated by designer drugs (DREADDs) represent a powerful chemogenetic technology for the remote control of neuronal activity and cellular signalling. The muscarinic receptor-based DREADDs are the most widely used chemogenetic tools in neuroscience research. The G-coupled DREADD (hM3Dq) is used to enhance neuronal activity, whereas the G-coupled DREADD (hM4Di) is utilized to inhibit neuronal activity. Here we report four DREADD-related cryogenic electron microscopy high-resolution structures: a hM3Dq-miniG complex and a hM4Di-miniG complex bound to deschloroclozapine; a hM3Dq-miniG complex bound to clozapine-N-oxide; and a hM3R-miniG complex bound to iperoxo. Complemented with mutagenesis, functional and computational simulation data, our structures reveal key details of the recognition of DREADD chemogenetic actuators and the molecular basis for activation. These findings should accelerate the structure-guided discovery of next-generation chemogenetic tools. 履歴 登録 2022年8月27日 - ヘッダ(付随情報) 公開 2022年11月30日 - マップ公開 2022年11月30日 - 更新 2022年12月21日 - 現状 2022年12月21日 処理サイト : RCSB / 状態 : 公開
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