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- PDB-7s8n: CryoEM structure of Gq-coupled MRGPRX2 with small molecule agonis... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7s8n | ||||||
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Title | CryoEM structure of Gq-coupled MRGPRX2 with small molecule agonist (R)-Zinc-3573 | ||||||
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![]() | SIGNALING PROTEIN / GPCR | ||||||
Function / homology | ![]() mast cell secretagogue receptor activity / mast cell activation / sleep / neuropeptide binding / mast cell degranulation / positive regulation of cytokinesis / sensory perception of pain / G protein-coupled receptor activity / Olfactory Signaling Pathway / Activation of the phototransduction cascade ...mast cell secretagogue receptor activity / mast cell activation / sleep / neuropeptide binding / mast cell degranulation / positive regulation of cytokinesis / sensory perception of pain / G protein-coupled receptor activity / 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 / 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 / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | ||||||
![]() | Cao, C. / Fay, J.F. / Gumpper, R.H. / Roth, B.L. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structure, function and pharmacology of human itch GPCRs. Authors: Can Cao / Hye Jin Kang / Isha Singh / He Chen / Chengwei Zhang / Wenlei Ye / Byron W Hayes / Jing Liu / Ryan H Gumpper / Brian J Bender / Samuel T Slocum / Brian E Krumm / Katherine Lansu / ...Authors: Can Cao / Hye Jin Kang / Isha Singh / He Chen / Chengwei Zhang / Wenlei Ye / Byron W Hayes / Jing Liu / Ryan H Gumpper / Brian J Bender / Samuel T Slocum / Brian E Krumm / Katherine Lansu / John D McCorvy / Wesley K Kroeze / Justin G English / Jeffrey F DiBerto / Reid H J Olsen / Xi-Ping Huang / Shicheng Zhang / Yongfeng Liu / Kuglae Kim / Joel Karpiak / Lily Y Jan / Soman N Abraham / Jian Jin / Brian K Shoichet / Jonathan F Fay / Bryan L Roth / ![]() ![]() Abstract: The MRGPRX family of receptors (MRGPRX1-4) is a family of mas-related G-protein-coupled receptors that have evolved relatively recently. Of these, MRGPRX2 and MRGPRX4 are key physiological and ...The MRGPRX family of receptors (MRGPRX1-4) is a family of mas-related G-protein-coupled receptors that have evolved relatively recently. Of these, MRGPRX2 and MRGPRX4 are key physiological and pathological mediators of itch and related mast cell-mediated hypersensitivity reactions. MRGPRX2 couples to both G and G in mast cells. Here we describe agonist-stabilized structures of MRGPRX2 coupled to G and G in ternary complexes with the endogenous peptide cortistatin-14 and with a synthetic agonist probe, respectively, and the development of potent antagonist probes for MRGPRX2. We also describe a specific MRGPRX4 agonist and the structure of this agonist in a complex with MRGPRX4 and G. Together, these findings should accelerate the structure-guided discovery of therapeutic agents for pain, itch and mast cell-mediated hypersensitivity. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 196.6 KB | Display | ![]() |
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PDB format | ![]() | 154.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 432.5 KB | Display | |
Data in CIF | ![]() | 1.6 MB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 24898MC ![]() 7s8lC ![]() 7s8mC ![]() 7s8oC ![]() 7s8pC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 1.6 TB Data #1: Unaligned multi-frame micrographs [micrographs - multiframe]) |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 2 types, 2 molecules BR
#1: Protein | Mass: 28084.832 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#4: Protein | Mass: 37146.957 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Guanine nucleotide-binding protein ... , 2 types, 2 molecules CD
#2: Protein | Mass: 37728.152 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Antibody / Non-polymers , 2 types, 2 molecules E![](data/chem/img/8IU.gif)
![](data/chem/img/8IU.gif)
#5: Antibody | Mass: 27409.588 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#6: Chemical | ChemComp-8IU / ( |
-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
Component | Name: MRGPRX2-Gq (R)-ZINC-3573 / Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES | ||||||||||||
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Molecular weight | Value: 150 kDa/nm / Experimental value: NO | ||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||
Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 45 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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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 318836 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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