+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-25729 | |||||||||
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Title | Structure of the human FPR2-Gi complex with fMLFII | |||||||||
Map data | FPR2 fmlfii | |||||||||
Sample |
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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 / 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 / immune response-regulating cell surface receptor signaling pathway / scavenger 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 / positive regulation of innate immune response / 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 / positive regulation of monocyte chemotaxis / 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 / cargo receptor activity / 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 / 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 / positive chemotaxis / tertiary granule membrane / 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 / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / specific granule membrane / positive regulation of superoxide anion generation / positive regulation of phagocytosis / regulation of mitotic spindle organization / cellular response to forskolin / cardiac muscle cell apoptotic process / astrocyte activation / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor inner segment / receptor-mediated endocytosis / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / calcium-mediated signaling / microglial cell activation / negative regulation of inflammatory response / 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 amyloid-beta / 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 Similarity search - Function | |||||||||
Biological species | Homo (humans) / Homo sapiens (human) / Rattus (rat) / Bos taurus (cattle) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Zhuang YW | |||||||||
Funding support | United States, 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_25729.map.gz | 28.7 MB | EMDB map data format | |
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Header (meta data) | emd-25729-v30.xml emd-25729.xml | 15.3 KB 15.3 KB | Display Display | EMDB header |
Images | emd_25729.png | 38 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-25729 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25729 | HTTPS FTP |
-Validation report
Summary document | emd_25729_validation.pdf.gz | 340.4 KB | Display | EMDB validaton report |
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Full document | emd_25729_full_validation.pdf.gz | 340 KB | Display | |
Data in XML | emd_25729_validation.xml.gz | 5.7 KB | Display | |
Data in CIF | emd_25729_validation.cif.gz | 6.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25729 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25729 | HTTPS FTP |
-Related structure data
Related structure data | 7t6vMC 7t6sC 7t6tC 7t6uC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_25729.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | FPR2 fmlfii | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.071 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : formylpeptide receptors FPR2 WITH FMLFII
Entire | Name: formylpeptide receptors FPR2 WITH FMLFII |
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Components |
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-Supramolecule #1: formylpeptide receptors FPR2 WITH FMLFII
Supramolecule | Name: formylpeptide receptors FPR2 WITH FMLFII / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: Homo (humans) |
-Macromolecule #1: N-formyl peptide receptor 2
Macromolecule | Name: N-formyl peptide receptor 2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 43.246332 KDa |
Recombinant expression | Organism: Spodoptera (butterflies/moths) |
Sequence | String: DYKDDDDVDM GQPGNGSAFL LAPNGSHAPD HDVTQQRDEE NLYFQGASME TNFSTPLNEY EEVSYESAGY TVLRILPLVV LGVTFVLGV LGNGLVIWVA GFRMTRTVTT ICYLNLALAD FSFTATLPFL IVSMAMGEKW PFGWFLCKLI HIVVDINLFG S VFLIGFIA ...String: DYKDDDDVDM GQPGNGSAFL LAPNGSHAPD HDVTQQRDEE NLYFQGASME TNFSTPLNEY EEVSYESAGY TVLRILPLVV LGVTFVLGV LGNGLVIWVA GFRMTRTVTT ICYLNLALAD FSFTATLPFL IVSMAMGEKW PFGWFLCKLI HIVVDINLFG S VFLIGFIA LDRCICVLHP VWAQNHRTVS LAMKVIVGPW ILALVLTLPV FLFLTTVTIP NGDTYCTFNF ASWGGTPEER LK VAITMLT ARGIIRFVIG FSLPMSIVAI CYGLIAAKIH KKGMIKSSRP LRVLTAVVAS FFICWFPFQL VALLGTVWLK EML FYGKYK IIDILVNPTS SLAFFNSCLN PMLYVFVGQD FRERLIHSLP TSLERALSED SAPTNDTAAN SASP |
-Macromolecule #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
Macromolecule | Name: Guanine nucleotide-binding protein G(i) subunit alpha-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.313863 KDa |
Recombinant expression | Organism: Spodoptera (butterflies/moths) |
Sequence | String: GCTLSAEDKA AVERSKMIDR NLREDGEKAA REVKLLLLGA GESGKSTIVK QMKIIHEAGY SEEECKQYKA VVYSNTIQSI IAIIRAMGR LKIDFGDSAR ADDARQLFVL AGAAEEGFMT AELAGVIKRL WKDSGVQACF NRSREYQLND SAAYYLNDLD R IAQPNYIP ...String: GCTLSAEDKA AVERSKMIDR NLREDGEKAA REVKLLLLGA GESGKSTIVK QMKIIHEAGY SEEECKQYKA VVYSNTIQSI IAIIRAMGR LKIDFGDSAR ADDARQLFVL AGAAEEGFMT AELAGVIKRL WKDSGVQACF NRSREYQLND SAAYYLNDLD R IAQPNYIP TQQDVLRTRV KTTGIVETHF TFKDLHFKMF DVGAQRSERK KWIHCFEGVT AIIFCVALSD YDLVLAEDEE MN RMHESMK LFDSICNNKW FTDTSIILFL NKKDLFEEKI KKSPLTICYP EYAGSNTYEE AAAYIQCQFE DLNKRKDTKE IYT HFTCST DTKNVQFVFD AVTDVIIKNN LKDCGLF |
-Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus (rat) |
Molecular weight | Theoretical: 39.020664 KDa |
Recombinant expression | Organism: Spodoptera (butterflies/moths) |
Sequence | String: HHHHHHHHMG SLLQSELDQL RQEAEQLKNQ IRDARKACAD ATLSQITNNI DPVGRIQMRT RRTLRGHLAK IYAMHWGTDS RLLVSASQD GKLIIWDSYT TNKVHAIPLR SSWVMTCAYA PSGNYVACGG LDNICSIYNL KTREGNVRVS RELAGHTGYL S CCRFLDDN ...String: HHHHHHHHMG SLLQSELDQL RQEAEQLKNQ IRDARKACAD ATLSQITNNI DPVGRIQMRT RRTLRGHLAK IYAMHWGTDS RLLVSASQD GKLIIWDSYT TNKVHAIPLR SSWVMTCAYA PSGNYVACGG LDNICSIYNL KTREGNVRVS RELAGHTGYL S CCRFLDDN QIVTSSGDTT CALWDIETGQ QTTTFTGHTG DVMSLSLAPD TRLFVSGACD ASAKLWDVRE GMCRQTFTGH ES DINAICF FPNGNAFATG SDDATCRLFD LRADQELMTY SHDNIICGIT SVSFSKSGRL LLAGYDDFNC NVWDALKADR AGV LAGHDN RVSCLGVTDD GMAVATGSWD SFLKIWN |
-Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Bos taurus (cattle) |
Molecular weight | Theoretical: 7.432554 KDa |
Recombinant expression | Organism: Spodoptera (butterflies/moths) |
Sequence | String: ASNNTASIAQ ARKLVEQLKM EANIDRIKVS KAAADLMAYC EAHAKEDPLL TPVPASENPF REKKFFC |
-Macromolecule #5: scFv16
Macromolecule | Name: scFv16 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus (rat) |
Molecular weight | Theoretical: 26.323324 KDa |
Recombinant expression | Organism: Spodoptera (butterflies/moths) |
Sequence | String: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS SGGGGSGGGG SGGGGSSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS SGGGGSGGGG SGGGGSSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPERFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL |
-Macromolecule #6: Synthetic peptide
Macromolecule | Name: Synthetic peptide / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo (humans) |
Molecular weight | Theoretical: 663.868 Da |
Sequence | String: (FME)LFII |
-Macromolecule #7: PALMITIC ACID
Macromolecule | Name: PALMITIC ACID / type: ligand / ID: 7 / Number of copies: 1 / Formula: PLM |
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Molecular weight | Theoretical: 256.424 Da |
Chemical component information | ChemComp-PLM: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.2 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 70.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 303372 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |