登録情報 データベース : EMDB / ID : EMD-27967 ダウンロードとリンクタイトル CryoEM structure of miniGo-coupled hM4Di in complex with DCZ マップデータCryoEM structure of miniGo-coupled hM4Di in complex with DCZ 詳細 試料複合体 : Gq-coupled hM3R complex複合体 : muscarinic acetylcholine receptor 4, miniGo 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 M4タンパク質・ペプチド : miniGo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 キーワード GPCR / DCZ / active state / MEMBRANE PROTEIN / hM4Di / DREADD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 / G protein-coupled acetylcholine receptor activity / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / vesicle docking involved in exocytosis / G protein-coupled dopamine receptor signaling pathway / regulation of locomotion / regulation of heart contraction / parallel fiber to Purkinje cell synapse ... Muscarinic acetylcholine receptors / G protein-coupled acetylcholine receptor activity / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / vesicle docking involved in exocytosis / G protein-coupled dopamine receptor signaling pathway / regulation of locomotion / regulation of heart contraction / parallel fiber to Purkinje cell synapse / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / 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 / 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 / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / 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 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / 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 / presynaptic membrane / cell body / 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 / G alpha (q) signalling events / 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 / Ras protein signal transduction / postsynaptic membrane / cell surface receptor signaling pathway / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / dendrite / GTP binding / protein-containing complex binding / glutamatergic synapse / signal transduction / extracellular exosome / metal ion binding / membrane / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 Muscarinic acetylcholine receptor M4 / Muscarinic acetylcholine receptor family / 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 ... Muscarinic acetylcholine receptor M4 / Muscarinic acetylcholine receptor family / 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 Guanine nucleotide-binding protein G(o) subunit alpha / Muscarinic acetylcholine receptor M4 / 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 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.7 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 2025年5月14日 - 現状 2025年5月14日 処理サイト : RCSB / 状態 : 公開
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