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Yorodumi- PDB-6omm: Cryo-EM structure of formyl peptide receptor 2/lipoxin A4 recepto... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6omm | |||||||||
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Title | Cryo-EM structure of formyl peptide receptor 2/lipoxin A4 receptor in complex with Gi | |||||||||
Components |
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Keywords | SIGNALING PROTEIN / Formyl peptide receptor 2/lipoxin A4 receptor / GPCR / Gi protein | |||||||||
Function / homology | Function and homology information N-formyl peptide receptor activity / complement receptor activity / immune response-regulating cell surface receptor signaling pathway / scavenger receptor binding / complement receptor mediated signaling pathway / positive regulation of innate immune response / Formyl peptide receptors bind formyl peptides and many other ligands / positive regulation of monocyte chemotaxis / cargo receptor activity / positive chemotaxis ...N-formyl peptide receptor activity / complement receptor activity / immune response-regulating cell surface receptor signaling pathway / scavenger receptor binding / complement receptor mediated signaling pathway / positive regulation of innate immune response / Formyl peptide receptors bind formyl peptides and many other ligands / positive regulation of monocyte chemotaxis / cargo receptor activity / positive chemotaxis / tertiary granule membrane / ficolin-1-rich granule membrane / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / specific granule membrane / positive regulation of phagocytosis / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / receptor-mediated endocytosis / positive regulation of superoxide anion generation / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / astrocyte activation / calcium-mediated signaling / microglial cell activation / 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) / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / negative regulation of inflammatory response / 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 / 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 / GPER1 signaling / GDP binding / cellular response to amyloid-beta / 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 / chemotaxis / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / signaling receptor activity / GTPase binding / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / amyloid-beta binding / cell cortex / midbody / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / cell adhesion / defense response to bacterium / cell cycle / inflammatory response / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / cell division Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) synthetic construct (others) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.17 Å | |||||||||
Authors | Zhuang, Y. / Liu, H. / de Waal, P.W. / Zhou, X.E. / Wang, L. / Meng, X. / Zhao, G. / Kang, Y. / Melcher, K. / Xu, H.E. / Zhang, C. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nat Commun / Year: 2020 Title: Structure of formylpeptide receptor 2-G complex reveals insights into ligand recognition and signaling. Authors: Youwen Zhuang / Heng Liu / X Edward Zhou / Ravi Kumar Verma / Parker W de Waal / Wonjo Jang / Ting-Hai Xu / Lei Wang / Xing Meng / Gongpu Zhao / Yanyong Kang / Karsten Melcher / Hao Fan / ...Authors: Youwen Zhuang / Heng Liu / X Edward Zhou / Ravi Kumar Verma / Parker W de Waal / Wonjo Jang / Ting-Hai Xu / Lei Wang / Xing Meng / Gongpu Zhao / Yanyong Kang / Karsten Melcher / Hao Fan / Nevin A Lambert / H Eric Xu / Cheng Zhang / Abstract: Formylpeptide receptors (FPRs) as G protein-coupled receptors (GPCRs) can recognize formylpeptides derived from pathogens or host cells to function in host defense and cell clearance. In addition, ...Formylpeptide receptors (FPRs) as G protein-coupled receptors (GPCRs) can recognize formylpeptides derived from pathogens or host cells to function in host defense and cell clearance. In addition, FPRs, especially FPR2, can also recognize other ligands with a large chemical diversity generated at different stages of inflammation to either promote or resolve inflammation in order to maintain a balanced inflammatory response. The mechanism underlying promiscuous ligand recognition and activation of FPRs is not clear. Here we report a cryo-EM structure of FPR2-G signaling complex with a peptide agonist. The structure reveals a widely open extracellular region with an amphiphilic environment for ligand binding. Together with computational docking and simulation, the structure suggests a molecular basis for the recognition of formylpeptides and a potential mechanism of receptor activation, and reveals conserved and divergent features in G coupling. Our results provide a basis for understanding the molecular mechanism of the functional promiscuity of FPRs. | |||||||||
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 | 6omm.cif.gz | 239.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6omm.ent.gz | 194.8 KB | Display | PDB format |
PDBx/mmJSON format | 6omm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/om/6omm ftp://data.pdbj.org/pub/pdb/validation_reports/om/6omm | HTTPS FTP |
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-Related structure data
Related structure data | 20126MC 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
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABC
#3: Protein | Mass: 40327.891 Da / Num. of mol.: 1 / Mutation: G203A, A326S, D328E 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 |
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#4: Protein | Mass: 39021.648 Da / Num. of mol.: 1 / Mutation: Q6E, E130Q, N237D 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 |
#5: Protein | Mass: 7430.584 Da / Num. of mol.: 1 / Mutation: E17Q, E58Q 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 |
-Protein / Protein/peptide / Antibody , 3 types, 3 molecules RLE
#1: Protein | Mass: 40329.238 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FPR2, FPRH1, FPRL1, LXA4R / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P25090 |
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#2: Protein/peptide | Mass: 857.117 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
#6: Antibody | Mass: 26323.324 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli) |
-Non-polymers , 2 types, 8 molecules
#7: Chemical | ChemComp-CLR / #8: Chemical | |
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-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 |
-Sample preparation
Component | Name: FPR2-Gi complex / Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.2 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: unspecified |
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: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 8.4 e/Å2 / Film or detector model: GATAN K2 BASE (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction | Resolution: 3.17 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1231594 / Symmetry type: POINT |