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Yorodumi- PDB-8jgg: CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist BAM8-22 -
+Open data
-Basic information
Entry | Database: PDB / ID: 8jgg | |||||||||
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Title | CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist BAM8-22 | |||||||||
Components |
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Keywords | STRUCTURAL PROTEIN / itch receptor / Mas-related GPCRs / MRGPRX1 | |||||||||
Function / homology | Function and homology information synaptic vesicle lumen / neuronal dense core vesicle lumen / response to chloroquine / chromaffin granule lumen / opioid receptor binding / opioid peptide activity / synaptic signaling via neuropeptide / general adaptation syndrome, behavioral process / aggressive behavior / positive regulation of behavioral fear response ...synaptic vesicle lumen / neuronal dense core vesicle lumen / response to chloroquine / chromaffin granule lumen / opioid receptor binding / opioid peptide activity / synaptic signaling via neuropeptide / general adaptation syndrome, behavioral process / aggressive behavior / positive regulation of behavioral fear response / G protein-coupled opioid receptor signaling pathway / symmetric synapse / cell body fiber / response to epinephrine / sensory perception / cellular response to vitamin D / neuropeptide hormone activity / locomotory exploration behavior / transmission of nerve impulse / startle response / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / neuropeptide signaling pathway / regulation of cAMP-mediated signaling / behavioral fear response / D2 dopamine receptor binding / glial cell proliferation / G protein-coupled serotonin receptor binding / axon terminus / regulation of mitotic spindle organization / cellular response to forskolin / cellular response to cAMP / sensory perception of pain / cellular response to transforming growth factor beta stimulus / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / response to nicotine / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / Post-translational protein phosphorylation / acute-phase response / 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-modulating 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 / Sensory perception of sweet, bitter, and umami (glutamate) taste / response to peptide hormone / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / response to toxic substance / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / osteoblast differentiation / cellular response to virus / 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 / response to calcium ion / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / sensory perception of taste / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / GPER1 signaling / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / G alpha (12/13) signalling events / transmembrane signaling receptor activity / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / response to estradiol / retina development in camera-type eye / GTPase binding / Ca2+ pathway / cellular response to oxidative stress / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | |||||||||
Authors | Sun, J.P. / Xu, H.E. / Ynag, F. / Liu, Z.M. / Guo, L.L. / Zhang, Y.M. / Fang, G.X. / Tie, L. / Zhuang, Y.M. / Xue, C.Y. | |||||||||
Funding support | China, 2items
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Citation | Journal: Nat Commun / Year: 2023 Title: Ligand recognition and G protein coupling of the human itch receptor MRGPRX1. Authors: Lulu Guo / Yumu Zhang / Guoxing Fang / Lu Tie / Yuming Zhuang / Chenyang Xue / Qi Liu / Minghui Zhang / Kongkai Zhu / Chongzhao You / Peiyu Xu / Qingning Yuan / Chao Zhang / Lei Liu / ...Authors: Lulu Guo / Yumu Zhang / Guoxing Fang / Lu Tie / Yuming Zhuang / Chenyang Xue / Qi Liu / Minghui Zhang / Kongkai Zhu / Chongzhao You / Peiyu Xu / Qingning Yuan / Chao Zhang / Lei Liu / Naikang Rong / Shengxuan Peng / Yuan Liu / Chuanzheng Wang / Xin Luo / Zongyao Lv / Dongwei Kang / Xiao Yu / Cheng Zhang / Yi Jiang / Xinzhong Dong / Jiuyao Zhou / Zhongmin Liu / Fan Yang / H Eric Xu / Jin-Peng Sun / Abstract: MRGPRX1, a Mas-related GPCR (MRGPR), is a key receptor for itch perception and targeting MRGPRX1 may have potential to treat both chronic itch and pain. Here we report cryo-EM structures of the ...MRGPRX1, a Mas-related GPCR (MRGPR), is a key receptor for itch perception and targeting MRGPRX1 may have potential to treat both chronic itch and pain. Here we report cryo-EM structures of the MRGPRX1-Gi1 and MRGPRX1-Gq trimers in complex with two peptide ligands, BAM8-22 and CNF-Tx2. These structures reveal a shallow orthosteric pocket and its conformational plasticity for sensing multiple different peptidic itch allergens. Distinct from MRGPRX2, MRGPRX1 contains a unique pocket feature at the extracellular ends of TM3 and TM4 to accommodate the peptide C-terminal "RF/RY" motif, which could serve as key mechanisms for peptidic allergen recognition. Below the ligand binding pocket, the GXPFGXF/W motif is essential for the inward tilting of the upper end of TM6 to induce receptor activation. Moreover, structural features inside the ligand pocket and on the cytoplasmic side of MRGPRX1 are identified as key elements for both Gi and Gq signaling. Collectively, our studies provide structural insights into understanding itch sensation, MRGPRX1 activation, and downstream G protein signaling. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8jgg.cif.gz | 220.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8jgg.ent.gz | 165.8 KB | Display | PDB format |
PDBx/mmJSON format | 8jgg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jg/8jgg ftp://data.pdbj.org/pub/pdb/validation_reports/jg/8jgg | HTTPS FTP |
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-Related structure data
Related structure data | 36233MC 8jgbC 8jgfC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules GAB
#1: Protein | Mass: 6633.625 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P59768 |
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#4: Protein | Mass: 40415.031 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63096 |
#5: Protein | Mass: 38561.152 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62873 |
-Protein/peptide / Antibody / Protein , 3 types, 3 molecules LSR
#2: Protein/peptide | Mass: 1603.797 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P01210 |
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#3: Antibody | Mass: 30363.043 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm) |
#6: Protein | Mass: 36276.906 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MRGPRX1, MRGX1, SNSR3, SNSR4 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q96LB2 |
-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: CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist BAM8-22 Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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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: FLOOD BEAM |
Electron lens | Mode: DIFFRACTION / Nominal defocus max: 1200 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 924644 / Symmetry type: POINT |