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Yorodumi- PDB-7vv4: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with... -
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-Basic information
Entry | Database: PDB / ID: 7vv4 | ||||||
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Title | Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with linear cortistatin-14, local | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / G Protein-Coupled Receptor | ||||||
Function / homology | Function and homology information mast cell secretagogue receptor activity / mast cell activation / neuropeptide hormone activity / sleep / neuropeptide binding / mast cell degranulation / positive regulation of cytokinesis / regulation of cell migration / sensory perception of pain / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway ...mast cell secretagogue receptor activity / mast cell activation / neuropeptide hormone activity / sleep / neuropeptide binding / mast cell degranulation / positive regulation of cytokinesis / regulation of cell migration / sensory perception of pain / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / G protein-coupled receptor binding / G protein-coupled receptor activity / G alpha (i) signalling events / chemical synaptic transmission / G protein-coupled receptor signaling pathway / synapse / extracellular space / extracellular region / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.97 Å | ||||||
Authors | Li, Y. / Yang, F. | ||||||
Funding support | China, 1items
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Citation | Journal: Nature / Year: 2021 Title: Structure, function and pharmacology of human itch receptor complexes. Authors: Fan Yang / Lulu Guo / Yu Li / Guopeng Wang / Jia Wang / Chao Zhang / Guo-Xing Fang / Xu Chen / Lei Liu / Xu Yan / Qun Liu / Changxiu Qu / Yunfei Xu / Peng Xiao / Zhongliang Zhu / Zijian Li / ...Authors: Fan Yang / Lulu Guo / Yu Li / Guopeng Wang / Jia Wang / Chao Zhang / Guo-Xing Fang / Xu Chen / Lei Liu / Xu Yan / Qun Liu / Changxiu Qu / Yunfei Xu / Peng Xiao / Zhongliang Zhu / Zijian Li / Jiuyao Zhou / Xiao Yu / Ning Gao / Jin-Peng Sun / Abstract: In the clades of animals that diverged from the bony fish, a group of Mas-related G-protein-coupled receptors (MRGPRs) evolved that have an active role in itch and allergic signals. As an MRGPR, ...In the clades of animals that diverged from the bony fish, a group of Mas-related G-protein-coupled receptors (MRGPRs) evolved that have an active role in itch and allergic signals. As an MRGPR, MRGPRX2 is known to sense basic secretagogues (agents that promote secretion) and is involved in itch signals and eliciting pseudoallergic reactions. MRGPRX2 has been targeted by drug development efforts to prevent the side effects induced by certain drugs or to treat allergic diseases. Here we report a set of cryo-electron microscopy structures of the MRGPRX2-G trimer in complex with polycationic compound 48/80 or with inflammatory peptides. The structures of the MRGPRX2-G complex exhibited shallow, solvent-exposed ligand-binding pockets. We identified key common structural features of MRGPRX2 and describe a consensus motif for peptidic allergens. Beneath the ligand-binding pocket, the unusual kink formation at transmembrane domain 6 (TM6) and the replacement of the general toggle switch from Trp to Gly (superscript annotations as per Ballesteros-Weinstein nomenclature) suggest a distinct activation process. We characterized the interfaces of MRGPRX2 and the G trimer, and mapped the residues associated with key single-nucleotide polymorphisms on both the ligand and G-protein interfaces of MRGPRX2. Collectively, our results provide a structural basis for the sensing of cationic allergens by MRGPRX2, potentially facilitating the rational design of therapies to prevent unwanted pseudoallergic reactions. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7vv4.cif.gz | 56.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7vv4.ent.gz | 42.9 KB | Display | PDB format |
PDBx/mmJSON format | 7vv4.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7vv4_validation.pdf.gz | 715.5 KB | Display | wwPDB validaton report |
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Full document | 7vv4_full_validation.pdf.gz | 720.8 KB | Display | |
Data in XML | 7vv4_validation.xml.gz | 15.6 KB | Display | |
Data in CIF | 7vv4_validation.cif.gz | 21.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vv/7vv4 ftp://data.pdbj.org/pub/pdb/validation_reports/vv/7vv4 | HTTPS FTP |
-Related structure data
Related structure data | 32137MC 7vdhC 7vdlC 7vdmC 7vuyC 7vuzC 7vv0C 7vv3C 7vv5C 7vv6C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 37123.984 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MRGPRX2, MRGX2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q96LB1 |
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#2: Protein/peptide | Mass: 1726.048 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: O00230 |
#3: Chemical | ChemComp-CLR / |
Has ligand of interest | N |
-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 | Name: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with linear cortistatin-14, local Type: COMPLEX / Entity ID: #1-#2 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.5 |
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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 58 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.97 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 303343 / Symmetry type: POINT |