+Open data
-Basic information
Entry | Database: PDB / ID: 7t6t | ||||||
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Title | Structure of the human FPR1-Gi complex with fMLFII | ||||||
Components |
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Keywords | SIGNALING PROTEIN / GPCR / membrane protein | ||||||
Function / homology | Function and homology information N-formyl peptide receptor activity / complement receptor activity / scavenger receptor binding / RAGE receptor binding / complement receptor mediated signaling pathway / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste ...N-formyl peptide receptor activity / complement receptor activity / scavenger receptor binding / RAGE receptor binding / complement receptor mediated signaling pathway / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / Formyl peptide receptors bind formyl peptides and many other ligands / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / azurophil granule membrane / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / Interleukin-10 signaling / ficolin-1-rich granule membrane / photoreceptor outer segment / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / nitric oxide mediated signal transduction / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / cardiac muscle cell apoptotic process / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor inner segment / secretory granule membrane / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / GPER1 signaling / GDP binding / chemotaxis / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / GTPase binding / retina development in camera-type eye / cellular response to hypoxia / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cell cortex / midbody / G alpha (i) signalling events / cell body / G alpha (s) signalling events / Extra-nuclear estrogen signaling Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Rattus (rat) Bos taurus (cattle) Homo (humans) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
Authors | Zhuang, Y.W. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Commun / Year: 2022 Title: Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2. Authors: Youwen Zhuang / Lei Wang / Jia Guo / Dapeng Sun / Yue Wang / Weiyi Liu / H Eric Xu / Cheng Zhang / Abstract: The formylpeptide receptors (FPRs) mediate pattern recognition of formylated peptides derived from invading pathogens or mitochondria from dead host cells. They can also sense other structurally ...The formylpeptide receptors (FPRs) mediate pattern recognition of formylated peptides derived from invading pathogens or mitochondria from dead host cells. They can also sense other structurally distinct native peptides and even lipid mediators to either promote or resolve inflammation. Pharmacological targeting of FPRs represents a novel therapeutic approach in treating inflammatory diseases. However, the molecular mechanisms underlying FPR ligand recognition are elusive. We report cryo-EM structures of G-coupled FPR1 and FPR2 bound to a formylpeptide and G-coupled FPR2 bound to two synthetic peptide and small-molecule agonists. Together with mutagenesis data, our structures reveal the molecular mechanism of formylpeptide recognition by FPRs and structural variations of FPR1 and FPR2 leading to their different ligand preferences. Structural analysis also suggests that diverse FPR agonists sample a conserved activation chamber at the bottom of ligand-binding pockets to activate FPRs. Our results provide a basis for rational drug design on FPRs. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7t6t.cif.gz | 171 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7t6t.ent.gz | 134.2 KB | Display | PDB format |
PDBx/mmJSON format | 7t6t.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7t6t_validation.pdf.gz | 765.7 KB | Display | wwPDB validaton report |
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Full document | 7t6t_full_validation.pdf.gz | 781.5 KB | Display | |
Data in XML | 7t6t_validation.xml.gz | 32 KB | Display | |
Data in CIF | 7t6t_validation.cif.gz | 47.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t6/7t6t ftp://data.pdbj.org/pub/pdb/validation_reports/t6/7t6t | HTTPS FTP |
-Related structure data
Related structure data | 25727MC 7t6sC 7t6uC 7t6vC 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 ABC
#1: Protein | Mass: 40313.863 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: Spodoptera (butterflies/moths) / References: UniProt: P63096 |
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#2: Protein | Mass: 39021.648 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus (rat) / Gene: Gnb1 / Production host: Spodoptera (butterflies/moths) / References: UniProt: P54311 |
#3: Protein | Mass: 7432.554 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNG2 / Production host: Spodoptera (butterflies/moths) / References: UniProt: P63212 |
-Protein/peptide / Protein / Non-polymers , 3 types, 4 molecules LR
#4: Protein/peptide | Mass: 663.868 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo (humans) |
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#5: Protein | Mass: 39041.699 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FPR1 / Production host: Spodoptera (butterflies/moths) / References: UniProt: P21462 |
#6: Chemical |
-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: formylpeptide receptors FPR1 / Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES | ||||||||||||||||
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Source (natural) |
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Source (recombinant) | Organism: Spodoptera (butterflies/moths) | ||||||||||||||||
Buffer solution | pH: 7.2 | ||||||||||||||||
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: BRIGHT FIELD / Nominal defocus max: 5000 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 70 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: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 258740 / Symmetry type: POINT |