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Yorodumi- PDB-7wvy: Cryo-EM structure of the human formyl peptide receptor 2 in compl... -
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-Basic information
Entry | Database: PDB / ID: 7wvy | ||||||||||||
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Title | Cryo-EM structure of the human formyl peptide receptor 2 in complex with Abeta42 and Gi2 | ||||||||||||
Components |
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Keywords | SIGNALING PROTEIN / G protein-coupled receptor / formyl peptide receptor / FPR2 / Abeta42 | ||||||||||||
Function / homology | Function and homology information N-formyl peptide receptor activity / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / complement receptor activity / immune response-regulating cell surface receptor signaling pathway / scavenger receptor binding / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / positive regulation of urine volume / complement receptor mediated signaling pathway / negative regulation of adenylate cyclase activity ...N-formyl peptide receptor activity / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / complement receptor activity / immune response-regulating cell surface receptor signaling pathway / scavenger receptor binding / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / positive regulation of urine volume / complement receptor mediated signaling pathway / negative regulation of adenylate cyclase activity / positive regulation of neural precursor cell proliferation / positive regulation of innate immune response / Formyl peptide receptors bind formyl peptides and many other ligands / gamma-aminobutyric acid signaling pathway / negative regulation of synaptic transmission / positive regulation of monocyte chemotaxis / cargo receptor activity / Golgi-associated vesicle / positive chemotaxis / neuronal dense core vesicle / tertiary granule membrane / regulation of calcium ion transport / negative regulation of apoptotic signaling pathway / ficolin-1-rich granule membrane / Adenylate cyclase inhibitory pathway / specific granule membrane / positive regulation of phagocytosis / positive regulation of insulin receptor signaling pathway / clathrin-coated pit / positive regulation of vascular associated smooth muscle cell proliferation / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / receptor-mediated endocytosis / response to nutrient / 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 / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Sensory perception of sweet, bitter, and umami (glutamate) taste / 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 / 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 / heparin binding / cell body / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / amyloid-beta binding / nervous system development / midbody / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / growth cone / fibroblast proliferation / perikaryon / G alpha (s) signalling events / G alpha (q) signalling events Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||||||||
Authors | Zhu, Y. / Lin, X. / Zong, X. / Han, S. / Zhao, Q. / Wu, B. | ||||||||||||
Funding support | China, 3items
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Citation | Journal: Nat Commun / Year: 2022 Title: Structural basis of FPR2 in recognition of Aβ and neuroprotection by humanin. Authors: Ya Zhu / Xiaowen Lin / Xin Zong / Shuo Han / Mu Wang / Yuxuan Su / Limin Ma / Xiaojing Chu / Cuiying Yi / Qiang Zhao / Beili Wu / Abstract: Formyl peptide receptor 2 (FPR2) has been shown to mediate the cytotoxic effects of the β amyloid peptide Aβ and serves as a receptor for humanin, a peptide that protects neuronal cells from damage ...Formyl peptide receptor 2 (FPR2) has been shown to mediate the cytotoxic effects of the β amyloid peptide Aβ and serves as a receptor for humanin, a peptide that protects neuronal cells from damage by Aβ, implying its involvement in the pathogenesis of Alzheimer's disease (AD). However, the interaction pattern between FPR2 and Aβ or humanin remains unknown. Here we report the structures of FPR2 bound to G and Aβ or N-formyl humanin (fHN). Combined with functional data, the structures reveal two critical regions that govern recognition and activity of Aβ and fHN, including a polar binding cavity within the receptor helical bundle and a hydrophobic binding groove in the extracellular region. In addition, the structures of FPR2 and FPR1 in complex with different formyl peptides were determined, providing insights into ligand recognition and selectivity of the FPR family. These findings uncover key factors that define the functionality of FPR2 in AD and other inflammatory diseases and would enable drug development. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7wvy.cif.gz | 179.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7wvy.ent.gz | 136.3 KB | Display | PDB format |
PDBx/mmJSON format | 7wvy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wv/7wvy ftp://data.pdbj.org/pub/pdb/validation_reports/wv/7wvy | HTTPS FTP |
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-Related structure data
Related structure data | 32862MC 7wvuC 7wvvC 7wvwC 7wvxC 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
#1: Protein/peptide | Mass: 4520.087 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: B4DMD5 |
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#2: Protein | Mass: 56710.328 Da / Num. of mol.: 1 / Mutation: S211L Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: cybC, FPR2, FPRH1, FPRL1, LXA4R / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P0ABE7, UniProt: P25090 |
#3: Protein | Mass: 40502.863 Da / Num. of mol.: 1 / Mutation: S47N, G204A, A327S, E246A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI2, GNAI2B / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P04899 |
#4: Protein | Mass: 38744.371 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 |
#5: Protein | Mass: 7861.143 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 |
-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: Formyl peptide receptor 2 in complex with Abeta42 and Gi2 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: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1500 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 2.1875 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1094657 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 60.15 Å2 | ||||||||||||||||||||||||
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