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Yorodumi- PDB-7yj4: Cryo-EM structure of the INSL5-bound human relaxin family peptide... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7yj4 | ||||||||||||||||||||||||||||||||||||
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Title | Cryo-EM structure of the INSL5-bound human relaxin family peptidereceptor 4 (RXFP4)-Gi complex | ||||||||||||||||||||||||||||||||||||
Components |
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Keywords | STRUCTURAL PROTEIN / human relaxin family peptide receptor 4 / G protein-coupled receptor / ligand recognition | ||||||||||||||||||||||||||||||||||||
Function / homology | Function and homology information Relaxin receptors / positive regulation of feeding behavior / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / positive regulation of urine volume / Activation of the phototransduction cascade ...Relaxin receptors / positive regulation of feeding behavior / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / positive regulation of urine volume / Activation of the phototransduction cascade / negative regulation of adenylate cyclase activity / G protein-coupled peptide receptor activity / positive regulation of neural precursor cell proliferation / gamma-aminobutyric acid signaling pathway / negative regulation of synaptic transmission / 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 / 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 / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / neuronal dense core vesicle / regulation of calcium ion transport / negative regulation of apoptotic signaling pathway / neuropeptide signaling pathway / Adenylate cyclase inhibitory pathway / response to nutrient / positive regulation of insulin receptor signaling pathway / positive regulation of superoxide anion generation / positive regulation of vascular associated smooth muscle cell proliferation / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Regulation of insulin secretion / G protein-coupled receptor binding / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / hormone activity / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / 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 / cellular response to prostaglandin E stimulus / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / extracellular vesicle / signaling receptor complex adaptor activity / midbody / G alpha (i) signalling events / cell body / G alpha (s) signalling events / Extra-nuclear estrogen signaling / cell population proliferation / positive regulation of ERK1 and ERK2 cascade / positive regulation of cell migration / G protein-coupled receptor signaling pathway / cell division / GTPase activity / centrosome / positive regulation of cell population proliferation / synapse / dendrite / GTP binding / signal transduction / extracellular exosome / extracellular region / nucleoplasm / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||||||||||||||||||||||||||||||||
Biological species | Homo sapiens (human) Bos taurus (cattle) synthetic construct (others) | ||||||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.19 Å | ||||||||||||||||||||||||||||||||||||
Authors | Chen, Y. / Zhou, Q.T. / Wang, J. / Xu, Y.W. / Wang, Y. / Yan, J.H. / Wang, Y.B. / Zhu, Q. / Zhao, F.H. / Li, C.H. ...Chen, Y. / Zhou, Q.T. / Wang, J. / Xu, Y.W. / Wang, Y. / Yan, J.H. / Wang, Y.B. / Zhu, Q. / Zhao, F.H. / Li, C.H. / Chen, C.W. / Cai, X.Q. / Bathgate, R.A.D. / Shen, C. / Liu, H. / Xu, H.E. / Yang, D.H. / Wang, M.W. | ||||||||||||||||||||||||||||||||||||
Funding support | China, 11items
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Citation | Journal: Nat Commun / Year: 2023 Title: Ligand recognition mechanism of the human relaxin family peptide receptor 4 (RXFP4). Authors: 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 ...Authors: 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 / Abstract: 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. | ||||||||||||||||||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7yj4.cif.gz | 211.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7yj4.ent.gz | 168 KB | Display | PDB format |
PDBx/mmJSON format | 7yj4.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7yj4_validation.pdf.gz | 1019.1 KB | Display | wwPDB validaton report |
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Full document | 7yj4_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7yj4_validation.xml.gz | 46 KB | Display | |
Data in CIF | 7yj4_validation.cif.gz | 69.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yj/7yj4 ftp://data.pdbj.org/pub/pdb/validation_reports/yj/7yj4 | HTTPS FTP |
-Related structure data
Related structure data | 33871MC 7yk6C 7yk7C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Insulin-like peptide INSL5 ... , 2 types, 2 molecules AB
#1: Protein/peptide | Mass: 2221.531 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: INSL5, UNQ156/PRO182 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9Y5Q6 |
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#2: Protein/peptide | Mass: 2850.365 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: INSL5, UNQ156/PRO182 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9Y5Q6 |
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules GIT
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63212 |
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#4: Protein | Mass: 40502.863 Da / Num. of mol.: 1 / Mutation: S47N,G204A,E246A,A327S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI2, GNAI2B / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P04899 |
#7: Protein | Mass: 37915.496 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62871 |
-Protein / Antibody , 2 types, 2 molecules RS
#5: Protein | Mass: 41177.270 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RXFP4, GPCR142, GPR100, RLN3R2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q8TDU9 |
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#6: Antibody | Mass: 26408.492 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Spodoptera frugiperda (fall armyworm) |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
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Source (natural) |
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Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) | ||||||||||||||||||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: OTHER / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 80 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.19 Å / Resolution method: DIFFRACTION PATTERN/LAYERLINES / Num. of particles: 52435 / Symmetry type: POINT |