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- PDB-7yk6: Cryo-EM structure of the compound 4-bound human relaxin family pe... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7yk6 | ||||||||||||||||||||||||||||||||||||
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Title | Cryo-EM structure of the compound 4-bound human relaxin family peptide receptor 4 (RXFP4)-Gi complex | ||||||||||||||||||||||||||||||||||||
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![]() | STRUCTURAL PROTEIN / human relaxin family peptide receptor 4 / G protein-coupled receptor / ligand recognition | ||||||||||||||||||||||||||||||||||||
Function / homology | ![]() Relaxin receptors / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / positive regulation of feeding behavior / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / positive regulation of urine volume / negative regulation of adenylate cyclase activity / C-C chemokine receptor activity / C-C chemokine binding / positive regulation of neural precursor cell proliferation ...Relaxin receptors / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / positive regulation of feeding behavior / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / positive regulation of urine volume / negative regulation of adenylate cyclase activity / C-C chemokine receptor activity / C-C chemokine binding / positive regulation of neural precursor cell proliferation / G protein-coupled peptide receptor activity / 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 / Adenylate cyclase inhibitory pathway / neuropeptide signaling pathway / positive regulation of insulin receptor signaling pathway / positive regulation of vascular associated smooth muscle cell proliferation / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to nutrient / cell chemotaxis / positive regulation of superoxide anion generation / Regulation of insulin secretion / G protein-coupled receptor binding / calcium-mediated signaling / G-protein beta/gamma-subunit complex binding / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / midbody / positive regulation of cytosolic calcium ion concentration / cell body / G alpha (i) signalling events Similarity search - Function | ||||||||||||||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() synthetic construct (others) | ||||||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.03 Å | ||||||||||||||||||||||||||||||||||||
![]() | 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 | ![]()
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 206.7 KB | Display | ![]() |
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PDB format | ![]() | 162.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
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Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 46.5 KB | Display | |
Data in CIF | ![]() | 69.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 33888MC ![]() 7yj4C ![]() 7yk7C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules GIT
#1: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#2: 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.) ![]() ![]() ![]() |
#5: Protein | Mass: 37915.496 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Protein / Antibody / Non-polymers , 3 types, 3 molecules RS![](data/chem/img/IYF.gif)
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#3: Protein | Mass: 41177.270 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#4: 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: ![]() ![]() |
#6: Chemical | ChemComp-IYF / |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Source (natural) |
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Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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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) |
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Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.03 Å / Resolution method: DIFFRACTION PATTERN/LAYERLINES / Num. of particles: 243800 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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