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Yorodumi- PDB-7vv0: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with... -
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-Basic information
Entry | Database: PDB / ID: 7vv0 | ||||||
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Title | Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, local | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / G Protein-Coupled Receptor | ||||||
Function / homology | Function and homology information adrenomedullin receptor binding / positive regulation of progesterone biosynthetic process / mast cell secretagogue receptor activity / vascular associated smooth muscle cell development / neuron projection regeneration / adrenomedullin receptor signaling pathway / mast cell activation / spongiotrophoblast layer development / Calcitonin-like ligand receptors / branching involved in labyrinthine layer morphogenesis ...adrenomedullin receptor binding / positive regulation of progesterone biosynthetic process / mast cell secretagogue receptor activity / vascular associated smooth muscle cell development / neuron projection regeneration / adrenomedullin receptor signaling pathway / mast cell activation / spongiotrophoblast layer development / Calcitonin-like ligand receptors / branching involved in labyrinthine layer morphogenesis / positive regulation of vasculogenesis / regulation of systemic arterial blood pressure / regulation of the force of heart contraction / sleep / neuropeptide binding / regulation of urine volume / G protein-coupled receptor internalization / negative regulation of vascular permeability / negative regulation of vasoconstriction / positive regulation of heart rate / mast cell degranulation / positive regulation of cytokinesis / response to starvation / odontogenesis of dentin-containing tooth / androgen metabolic process / developmental growth / vasculogenesis / animal organ regeneration / response to glucocorticoid / sensory perception of pain / cAMP-mediated signaling / neural tube closure / G protein-coupled receptor activity / female pregnancy / response to insulin / adenylate cyclase-activating G protein-coupled receptor signaling pathway / hormone activity / receptor internalization / positive regulation of angiogenesis / heart development / positive regulation of cytosolic calcium ion concentration / G alpha (s) signalling events / cell population proliferation / response to lipopolysaccharide / response to hypoxia / inflammatory response / positive regulation of apoptotic process / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / signaling receptor binding / positive regulation of cell population proliferation / signal transduction / extracellular space / extracellular region / membrane / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 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 | 7vv0.cif.gz | 56.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7vv0.ent.gz | 42.8 KB | Display | PDB format |
PDBx/mmJSON format | 7vv0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7vv0_validation.pdf.gz | 723.1 KB | Display | wwPDB validaton report |
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Full document | 7vv0_full_validation.pdf.gz | 729.2 KB | Display | |
Data in XML | 7vv0_validation.xml.gz | 15.8 KB | Display | |
Data in CIF | 7vv0_validation.cif.gz | 21.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vv/7vv0 ftp://data.pdbj.org/pub/pdb/validation_reports/vv/7vv0 | HTTPS FTP |
-Related structure data
Related structure data | 32133MC 7vdhC 7vdlC 7vdmC 7vuyC 7vuzC 7vv3C 7vv4C 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/peptide | Mass: 1624.952 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P35318 |
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#2: 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 |
#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 PAMP-12, 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: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 978001 / Symmetry type: POINT |