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- EMDB-32133: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-32133 | |||||||||
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Title | Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, local | |||||||||
![]() | Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, local | |||||||||
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Function / homology | ![]() 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 | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
![]() | Li Y / Yang F | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 29.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.2 KB 11.2 KB | Display Display | ![]() |
Images | ![]() | 25.6 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 310.8 KB | Display | ![]() |
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Full document | ![]() | 310.4 KB | Display | |
Data in XML | ![]() | 5.5 KB | Display | |
Data in CIF | ![]() | 6.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7vv0MC ![]() 7vdhC ![]() 7vdlC ![]() 7vdmC ![]() 7vuyC ![]() 7vuzC ![]() 7vv3C ![]() 7vv4C ![]() 7vv5C ![]() 7vv6C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, local | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.8286 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with...
Entire | Name: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, local |
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Components |
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-Supramolecule #1: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with...
Supramolecule | Name: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, local type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: peptide from Pro-adrenomedullin
Macromolecule | Name: peptide from Pro-adrenomedullin / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 1.624952 KDa |
Sequence | String: FRKKWNKWAL SR |
-Macromolecule #2: Mas-related G-protein coupled receptor member X2
Macromolecule | Name: Mas-related G-protein coupled receptor member X2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 37.123984 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MDPTTPAWGT ESTTVNGNDQ ALLLLCGKET LIPVFLILFI ALVGLVGNGF VLWLLGFRMR RNAFSVYVLS LAGADFLFLC FQIINCLVY LSNFFCSISI NFPSFFTTVM TCAYLAGLSM LSTVSTERCL SVLWPIWYRC RRPRHLSAVV CVLLWALSLL L SILEGKFC ...String: MDPTTPAWGT ESTTVNGNDQ ALLLLCGKET LIPVFLILFI ALVGLVGNGF VLWLLGFRMR RNAFSVYVLS LAGADFLFLC FQIINCLVY LSNFFCSISI NFPSFFTTVM TCAYLAGLSM LSTVSTERCL SVLWPIWYRC RRPRHLSAVV CVLLWALSLL L SILEGKFC GFLFSDGDSG WCQTFDFITA AWLIFLFMVL CGSSLALLVR ILCGSRGLPL TRLYLTILLT VLVFLLCGLP FG IQWFLIL WIWKDSDVLF CHIHPVSVVL SSLNSSANPI IYFFVGSFRK QWRLQQPILK LALQRALQDI AEVDHSEGCF RQG TPEMSR SSLV |
-Macromolecule #3: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 3 / Number of copies: 1 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 58.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 978001 |
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Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |