- EMDB-24733: Oxytocin receptor (OTR) bound to oxytocin in complex with a heter... -
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データベース: EMDB / ID: EMD-24733
タイトル
Oxytocin receptor (OTR) bound to oxytocin in complex with a heterotrimeric Gq protein
マップデータ
Combined map from local refinements
試料
複合体: Oxytocin receptor signaling complex with oxytocin and miniGq and an scFv
複合体: Oxytocin
タンパク質・ペプチド: Oxytocin
複合体: Oxytocin receptor
タンパク質・ペプチド: Oxytocin receptor
複合体: miniGq
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
複合体: scFv16
タンパク質・ペプチド: scFv16
リガンド: MAGNESIUM ION
キーワード
HORMONE / GPCR COMPLEX / TRANSMEMBRANE RECEPTOR / OXYTOCIN RECEPTOR / OTR / OT / OXTR / G PROTEIN / OXYTOCIN / VASOTOCIN / MEMBRANE PROTEIN / MEMBRANE PROTEIN-NEUROPEPTIDE complex
機能・相同性
機能・相同性情報
oxytocin receptor activity / positive regulation of hindgut contraction / maternal aggressive behavior / oxytocin receptor binding / neurohypophyseal hormone activity / V1A vasopressin receptor binding / sperm ejaculation / positive regulation of penile erection / positive regulation of uterine smooth muscle contraction / Vasopressin-like receptors ...oxytocin receptor activity / positive regulation of hindgut contraction / maternal aggressive behavior / oxytocin receptor binding / neurohypophyseal hormone activity / V1A vasopressin receptor binding / sperm ejaculation / positive regulation of penile erection / positive regulation of uterine smooth muscle contraction / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / maternal process involved in parturition / negative regulation of urine volume / positive regulation of norepinephrine secretion / response to sucrose / drinking behavior / response to ether / positive regulation of prostaglandin secretion / grooming behavior / positive regulation of blood pressure / neuropeptide hormone activity / maternal behavior / positive regulation of ossification / positive regulation of female receptivity / positive regulation of synapse assembly / eating behavior / response to food / male mating behavior / positive regulation of vasoconstriction / response to electrical stimulus / social behavior / response to cAMP / positive regulation of synaptic transmission / response to retinoic acid / neuronal dense core vesicle / cellular response to hormone stimulus / negative regulation of blood pressure / response to prostaglandin E / lactation / muscle contraction / regulation of heart rate / response to glucocorticoid / response to progesterone / secretory granule / response to amphetamine / response to activity / response to cocaine / female pregnancy / response to peptide hormone / memory / 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 / terminal bouton / 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 / 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 / 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 / response to estradiol / 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) / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / heart development / positive regulation of cytosolic calcium ion concentration / GTPase binding / Ca2+ pathway / 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 類似検索 - 分子機能
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
T32-GM089626
米国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2022 タイトル: The oxytocin signaling complex reveals a molecular switch for cation dependence. 著者: Justin G Meyerowitz / Michael J Robertson / Ximena Barros-Álvarez / Ouliana Panova / Robert M Nwokonko / Yang Gao / Georgios Skiniotis / 要旨: Oxytocin (OT) and vasopressin (AVP) are conserved peptide signaling hormones that are critical for diverse processes including osmotic homeostasis, reproduction, lactation and social interaction. OT ...Oxytocin (OT) and vasopressin (AVP) are conserved peptide signaling hormones that are critical for diverse processes including osmotic homeostasis, reproduction, lactation and social interaction. OT acts through the oxytocin receptor (OTR), a magnesium-dependent G protein-coupled receptor that is a therapeutic target for treatment of postpartum hemorrhage, dysfunctional labor and autism. However, the molecular mechanisms that underlie OTR activation by OT and the dependence on magnesium remain unknown. Here we present the wild-type active-state structure of human OTR bound to OT and miniG determined by cryo-EM. The structure reveals a unique activation mechanism adopted by OTR involving both the formation of a Mg coordination complex between OT and the receptor, and disruption of transmembrane helix 7 (TM7) by OT. Our functional assays demonstrate the role of TM7 disruption and provide the mechanism of full agonism by OT and partial agonism by OT analogs. Furthermore, we find that the identity of a single cation-coordinating residue across vasopressin family receptors determines whether the receptor is cation-dependent. Collectively, these results demonstrate how the Mg-dependent OTR is activated by OT, provide essential information for structure-based drug discovery efforts and shed light on the molecular determinants of cation dependence of vasopressin family receptors throughout the animal kingdom.
EMPIAR-10936 (タイトル: Oxytocin receptor (OTR) bound to oxytocin in complex with a heterotrimeric Gq protein Data size: 4.1 TB Data #1: Unaligned multi-frame micrographs of the oxytocin-oxytocin receptor-miniGq complex [micrographs - multiframe])
全体 : Oxytocin receptor signaling complex with oxytocin and miniGq and ...
全体
名称: Oxytocin receptor signaling complex with oxytocin and miniGq and an scFv
要素
複合体: Oxytocin receptor signaling complex with oxytocin and miniGq and an scFv
複合体: Oxytocin
タンパク質・ペプチド: Oxytocin
複合体: Oxytocin receptor
タンパク質・ペプチド: Oxytocin receptor
複合体: miniGq
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
複合体: scFv16
タンパク質・ペプチド: scFv16
リガンド: MAGNESIUM ION
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超分子 #1: Oxytocin receptor signaling complex with oxytocin and miniGq and ...
超分子
名称: Oxytocin receptor signaling complex with oxytocin and miniGq and an scFv タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5