登録情報 データベース : EMDB / ID : EMD-36144 ダウンロードとリンクタイトル Senktide bound to active human neurokinin 3 receptor in complex with Gq マップデータSenktide bound to active human neurokinin 3 receptor in complex with Gq 詳細 試料複合体 : Senktide bound to active human neurokinin 3 receptor in complex with Gq heterotrimerタンパク質・ペプチド : Neuromedin-K receptor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 : ScFv16 nanobodyタンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2タンパク質・ペプチド : Senktideタンパク質・ペプチド : Guanine nucleotide-binding protein Gq subunit alpha 残り2件を表示 表示を減らす 詳細 キーワード G protein coupled receptor / Neurokinin / Cryo-EM / Peptide Agonists / MEMBRANE 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
tachykinin receptor activity / Tachykinin receptors bind tachykinins / positive regulation of flagellated sperm motility / positive regulation of uterine smooth muscle contraction / tachykinin receptor signaling pathway / regulation of feeding behavior / regulation of dopamine metabolic process / positive regulation of blood pressure / G-protein activation / Activation of the phototransduction cascade ... tachykinin receptor activity / Tachykinin receptors bind tachykinins / positive regulation of flagellated sperm motility / positive regulation of uterine smooth muscle contraction / tachykinin receptor signaling pathway / regulation of feeding behavior / regulation of dopamine metabolic process / positive regulation of blood pressure / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / alkylglycerophosphoethanolamine phosphodiesterase activity / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / positive regulation of heart rate / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / neuronal cell body membrane / photoreceptor outer segment / sperm midpiece / cardiac muscle cell apoptotic process / dendrite membrane / photoreceptor inner segment / response to cocaine / cellular response to catecholamine stimulus / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / GTPase binding / response to estradiol / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cell body / cellular response to hypoxia / G alpha (q) signalling events / cell population proliferation / G protein-coupled receptor signaling pathway / GTPase activity / dendrite / protein-containing complex binding / membrane / plasma membrane / cytoplasm 類似検索 - 分子機能 Neurokinin NK3 receptor / Neurokinin receptor / 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 ... Neurokinin NK3 receptor / Neurokinin receptor / 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 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily 類似検索 - ドメイン・相同性 Neuromedin-K receptor / 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 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Rattus norvegicus (ドブネズミ) / Mus musculoides (ネズミ) / Bos taurus (ウシ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.0 Å 詳細 データ登録者Sun WJ / Yang F / Zhang HH / Yuan QN / Yin WC / Shi P / Eric X / Tian CL 資金援助 中国, 1件 詳細 詳細を隠すOrganization Grant number 国 Other government 中国
引用ジャーナル : Cell Discov / 年 : 2023タイトル : Structural insights into neurokinin 3 receptor activation by endogenous and analogue peptide agonists.著者 : Wenjing Sun / Fan Yang / Huanhuan Zhang / Qingning Yuan / Shenglong Ling / Yuanxia Wang / Pei Lv / Zelin Li / Yifan Luo / Dongsheng Liu / Wanchao Yin / Pan Shi / H Eric Xu / Changlin Tian / 要旨 : Neurokinin 3 receptor (NK3R) is a tachykinin receptor essential for the hypothalamic-pituitary-gonadal axis. The endogenous peptide agonist neurokinin B (NKB) preferentially activates NK3R, while ... Neurokinin 3 receptor (NK3R) is a tachykinin receptor essential for the hypothalamic-pituitary-gonadal axis. The endogenous peptide agonist neurokinin B (NKB) preferentially activates NK3R, while substance P (SP) binds preferentially to NK1R. In addition, the SP analogue senktide more potently activates NK3R than NKB and SP. However, the mechanisms of preferential binding of peptide and NK3R activation remain elusive. Herein, we determined the cryogenic electron microscopy (cryo-EM) structures of the NK3R-G complex bound to NKB, SP and senktide. The three NK3R-G/peptide complexes utilize a class of noncanonical receptor activation mechanisms. Combining the structural analysis and functional assay illustrated that the consensus C-termini of the three peptide agonists share a conserved binding mode to NK3R, while the divergent N-termini of the peptides confer the preferential binding of the agonist to NK3R. In addition, the specific interactions between the N-terminus of senktide and the N-terminus and extracellular loops (ECL2 and ECL3) of NK3R lead to the improved activation displayed by senktide compared to SP and NKB. These findings pave the way to understand tachykinin receptor subtype selectivity and provide ideas to rationally develop drugs targeting NK3R. 履歴 登録 2023年5月8日 - ヘッダ(付随情報) 公開 2024年2月28日 - マップ公開 2024年2月28日 - 更新 2024年2月28日 - 現状 2024年2月28日 処理サイト : PDBj / 状態 : 公開
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