登録情報 データベース : EMDB / ID : EMD-33871 ダウンロードとリンクタイトル Cryo-EM structure of the INSL5-bound human relaxin family peptidereceptor 4(RXFP4)-Gi complex マップデータ 詳細 試料複合体 : Cryo-EM structure of the human relaxin family peptide receptor 4 in complex with INSL5 and G protein複合体 : INSL5タンパク質・ペプチド : Insulin-like peptide INSL5 A chainタンパク質・ペプチド : Insulin-like peptide INSL5 B chain複合体 : human relaxin family peptide receptor 4タンパク質・ペプチド : Relaxin-3 receptor 2複合体 : G protein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 : Guanine nucleotide-binding protein G(i) subunit alpha-2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 詳細 キーワード human relaxin family peptide receptor 4 / G protein-coupled receptor / ligand recognition / STRUCTURAL 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
Relaxin receptors / galanin receptor activity / positive regulation of feeding behavior / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / negative regulation of calcium ion-dependent exocytosis / G protein-coupled adenosine receptor signaling pathway / Activation of the phototransduction cascade ... Relaxin receptors / galanin receptor activity / positive regulation of feeding behavior / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / negative regulation of calcium ion-dependent exocytosis / G protein-coupled adenosine receptor signaling pathway / Activation of the phototransduction cascade / negative regulation of adenylate cyclase activity / positive regulation of neural precursor cell proliferation / negative regulation of synaptic transmission / positive regulation of urine volume / 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 / G alpha (12/13) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / G alpha (z) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins / gamma-aminobutyric acid signaling pathway / regulation of calcium ion transport / negative regulation of apoptotic signaling pathway / neuronal dense core vesicle / positive regulation of vascular associated smooth muscle cell proliferation / positive regulation of superoxide anion generation / Adenylate cyclase inhibitory pathway / response to nutrient / hippocampal mossy fiber to CA3 synapse / Regulation of insulin secretion / neuropeptide signaling pathway / hormone activity / G protein-coupled receptor binding / G-protein beta/gamma-subunit complex binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G-protein beta-subunit binding / extracellular vesicle / sensory perception of taste / adenylate cyclase-activating G protein-coupled receptor signaling pathway / signaling receptor complex adaptor activity / retina development in camera-type eye / cell body / GTPase binding / midbody / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / 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 / positive regulation of ERK1 and ERK2 cascade / cell population proliferation / Extra-nuclear estrogen signaling / ciliary basal body / positive regulation of cell migration / G protein-coupled receptor signaling pathway / cell division / GTPase activity / positive regulation of cell population proliferation / centrosome / synapse / dendrite / GTP binding / protein-containing complex binding / signal transduction / extracellular exosome / extracellular region / nucleoplasm / membrane / metal ion binding / plasma membrane 類似検索 - 分子機能 : / Angiotensin II receptor family / : / Insulin-like / Insulin/IGF/Relaxin family / Insulin / insulin-like growth factor / relaxin family. / Insulin, conserved site / Insulin family signature. / Insulin-like superfamily / G-protein alpha subunit, group I ... : / Angiotensin II receptor family / : / Insulin-like / Insulin/IGF/Relaxin family / Insulin / insulin-like growth factor / relaxin family. / Insulin, conserved site / Insulin family signature. / Insulin-like superfamily / G-protein alpha subunit, group I / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / 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 / 7 transmembrane receptor (rhodopsin family) / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 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(i) subunit alpha-2 / 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 / Relaxin-3 receptor 2 / Insulin-like peptide INSL5 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / synthetic construct (人工物) / 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 : 3.19 Å 詳細 データ登録者Chen Y / Zhou QT / Wang J / Xu YW / Wang Y / Yan JH / Wang YB / Zhu Q / Zhao FH / Li CH ...Chen Y / Zhou QT / Wang J / Xu YW / Wang Y / Yan JH / Wang YB / Zhu Q / Zhao FH / Li CH / Chen CW / Cai XQ / Bathgate RAD / Shen C / Liu H / Xu HE / Yang DH / Wang MW 資金援助 中国, 11件 詳細 詳細を隠すOrganization Grant number 国 National Natural Science Foundation of China (NSFC) 81872915 中国 National Natural Science Foundation of China (NSFC) 82073904 中国 National Natural Science Foundation of China (NSFC) 82121005 中国 National Natural Science Foundation of China (NSFC) 81973373 中国 National Natural Science Foundation of China (NSFC) 82130105 中国 National Natural Science Foundation of China (NSFC) 21704064 中国 Other government 2021ZD0203400 Other government 2018YFA0507000 Other government ZDKJ2021028 Other government 21JC1401600 Other government 1135837
引用ジャーナル : Nat Commun / 年 : 2023タイトル : Ligand recognition mechanism of the human relaxin family peptide receptor 4 (RXFP4).著者: Yan Chen / Qingtong Zhou / Jiang Wang / Youwei Xu / Yun Wang / Jiahui Yan / Yibing Wang / Qi Zhu / Fenghui Zhao / Chenghao Li / Chuan-Wei Chen / Xiaoqing Cai / Ross A D Bathgate / Chun Shen / ... 著者 : Yan Chen / Qingtong Zhou / Jiang Wang / Youwei Xu / Yun Wang / Jiahui Yan / Yibing Wang / Qi Zhu / Fenghui Zhao / Chenghao Li / Chuan-Wei Chen / Xiaoqing Cai / Ross A D Bathgate / Chun Shen / H Eric Xu / Dehua Yang / Hong Liu / Ming-Wei Wang / 要旨 : Members of the insulin superfamily regulate pleiotropic biological processes through two types of target-specific but structurally conserved peptides, insulin/insulin-like growth factors and ... Members of the insulin superfamily regulate pleiotropic biological processes through two types of target-specific but structurally conserved peptides, insulin/insulin-like growth factors and relaxin/insulin-like peptides. The latter bind to the human relaxin family peptide receptors (RXFPs). Here, we report three cryo-electron microscopy structures of RXFP4-G protein complexes in the presence of the endogenous ligand insulin-like peptide 5 (INSL5) or one of the two small molecule agonists, compound 4 and DC591053. The B chain of INSL5 adopts a single α-helix that penetrates into the orthosteric pocket, while the A chain sits above the orthosteric pocket, revealing a peptide-binding mode previously unknown. Together with mutagenesis and functional analyses, the key determinants responsible for the peptidomimetic agonism and subtype selectivity were identified. Our findings not only provide insights into ligand recognition and subtype selectivity among class A G protein-coupled receptors, but also expand the knowledge of signaling mechanisms in the insulin superfamily. 履歴 登録 2022年7月19日 - ヘッダ(付随情報) 公開 2023年3月1日 - マップ公開 2023年3月1日 - 更新 2024年10月23日 - 現状 2024年10月23日 処理サイト : PDBj / 状態 : 公開
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