- EMDB-24733: Oxytocin receptor (OTR) bound to oxytocin in complex with a heter... -
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基本情報
登録情報
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 / response to anoxia / oxytocin receptor binding / neurohypophyseal hormone activity / V1A vasopressin receptor binding / sperm ejaculation / positive regulation of penile erection / positive regulation of uterine smooth muscle contraction ...oxytocin receptor activity / positive regulation of hindgut contraction / maternal aggressive behavior / response to anoxia / 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 / positive regulation of norepinephrine secretion / negative regulation of urine volume / drinking behavior / response to sucrose / telencephalon development / 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 / digestive tract development / positive regulation of synapse assembly / eating behavior / response to food / male mating behavior / suckling behavior / neuronal dense core vesicle / microvillus / peptide hormone binding / social behavior / response to electrical stimulus / positive regulation of synaptic transmission / response to glucocorticoid / response to retinoic acid / estrous cycle / positive regulation of vasoconstriction / response to cAMP / cellular response to hormone stimulus / response to prostaglandin E / lactation / negative regulation of blood pressure / ERK1 and ERK2 cascade / response to cytokine / ionotropic glutamate receptor binding / response to amphetamine / muscle contraction / positive regulation of synaptic transmission, glutamatergic / regulation of heart rate / secretory granule / female pregnancy / response to progesterone / response to activity / positive regulation of synaptic transmission, GABAergic / adherens junction / response to cocaine / response to peptide hormone / 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 / terminal bouton / G protein-coupled acetylcholine receptor signaling pathway / memory / 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 / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / 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 / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle 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