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Yorodumi- EMDB-32862: Cryo-EM structure of the human formyl peptide receptor 2 in compl... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32862 | ||||||||||||
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Title | Cryo-EM structure of the human formyl peptide receptor 2 in complex with Abeta42 and Gi2 | ||||||||||||
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Sample |
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Function / homology | Function and homology information N-formyl peptide receptor activity / complement receptor activity / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / 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 / complement receptor activity / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / 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 / positive regulation of monocyte chemotaxis / gamma-aminobutyric acid signaling pathway / negative regulation of synaptic transmission / cargo receptor activity / Golgi-associated vesicle / positive chemotaxis / neuronal dense core vesicle / regulation of calcium ion transport / tertiary granule membrane / negative regulation of apoptotic signaling pathway / ficolin-1-rich granule membrane / Adenylate cyclase inhibitory pathway / specific granule membrane / response to nutrient / positive regulation of insulin receptor signaling pathway / positive regulation of superoxide anion generation / clathrin-coated pit / positive regulation of phagocytosis / positive regulation of vascular associated smooth muscle cell proliferation / astrocyte activation / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / receptor-mediated endocytosis / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / electron transport chain / calcium-mediated signaling / microglial cell activation / negative regulation of inflammatory 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-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / 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 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / 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 / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to amyloid-beta / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / chemotaxis / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / signaling receptor activity / nervous system development / heparin binding / phospholipase C-activating G protein-coupled receptor signaling pathway / amyloid-beta binding / positive regulation of cytosolic calcium ion concentration / midbody / G alpha (i) signalling events / cell body / growth cone / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | ||||||||||||
Authors | Zhu Y / Lin X / Zong X / Han S / Zhao Q / Wu B | ||||||||||||
Funding support | China, 3 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_32862.map.gz | 5.1 MB | EMDB map data format | |
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Header (meta data) | emd-32862-v30.xml emd-32862.xml | 14.9 KB 14.9 KB | Display Display | EMDB header |
Images | emd_32862.png | 27.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32862 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32862 | HTTPS FTP |
-Validation report
Summary document | emd_32862_validation.pdf.gz | 337.6 KB | Display | EMDB validaton report |
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Full document | emd_32862_full_validation.pdf.gz | 337.2 KB | Display | |
Data in XML | emd_32862_validation.xml.gz | 6 KB | Display | |
Data in CIF | emd_32862_validation.cif.gz | 6.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32862 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32862 | HTTPS FTP |
-Related structure data
Related structure data | 7wvyMC 7wvuC 7wvvC 7wvwC 7wvxC 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_32862.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.045 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : Formyl peptide receptor 2 in complex with Abeta42 and Gi2
Entire | Name: Formyl peptide receptor 2 in complex with Abeta42 and Gi2 |
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Components |
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-Supramolecule #1: Formyl peptide receptor 2 in complex with Abeta42 and Gi2
Supramolecule | Name: Formyl peptide receptor 2 in complex with Abeta42 and Gi2 type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Macromolecule #1: Amyloid-beta A4 protein
Macromolecule | Name: Amyloid-beta A4 protein / 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: 4.520087 KDa |
Sequence | String: DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA IIGLMVGGVV IA |
-Macromolecule #2: Soluble cytochrome b562,N-formyl peptide receptor 2
Macromolecule | Name: Soluble cytochrome b562,N-formyl peptide receptor 2 / 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: 56.710328 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: GAPADLEDNW ETLNDNLKVI EKADNAAQVK DALTKMRAAA LDAQKATPPK LEDKSPDSPE MKDFRHGFDI LVGQIDDALK LANEGKVKE AQAAAEQLKT TRNAYIQKYL GSGSENLYFQ SETNFSTPLN EYEEVSYESA GYTVLRILPL VVLGVTFVLG V LGNGLVIW ...String: GAPADLEDNW ETLNDNLKVI EKADNAAQVK DALTKMRAAA LDAQKATPPK LEDKSPDSPE MKDFRHGFDI LVGQIDDALK LANEGKVKE AQAAAEQLKT TRNAYIQKYL GSGSENLYFQ SETNFSTPLN EYEEVSYESA GYTVLRILPL VVLGVTFVLG V LGNGLVIW VAGFRMTRTV TTICYLNLAL ADFSFTATLP FLIVSMAMGE KWPFGWFLCK LIHIVVDINL FGSVFLIGFI AL DRCICVL HPVWAQNHRT VSLAMKVIVG PWILALVLTL PVFLFLTTVT IPNGDTYCTF NFASWGGTPE ERLKVAITML TAR GIIRFV IGFLLPMSIV AICYGLIAAK IHKKGMIKSS RPLRVLTAVV ASFFICWFPF QLVALLGTVW LKEMLFYGKY KIID ILVNP TSSLAFFNSC LNPMLYVFVG QDFRERLIHS LPTSLERALS EDSAPTNDTA ANSASPPAET EFLEVLFQGP GSWSH PQFE KGSGAGASAG SWSHPQFEKG SDYKDDDDK |
-Macromolecule #3: Guanine nucleotide-binding protein G(i) subunit alpha-2
Macromolecule | Name: Guanine nucleotide-binding protein G(i) subunit alpha-2 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.502863 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGCTVSAEDK AAAERSKMID KNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEDG YSEEECRQYR AVVYSNTIQS IMAIVKAMG NLQIDFADPS RADDARQLFA LSCTAEEQGV LPDDLSGVIR RLWADHGVQA CFGRSREYQL NDSAAYYLND L ERIAQSDY ...String: MGCTVSAEDK AAAERSKMID KNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEDG YSEEECRQYR AVVYSNTIQS IMAIVKAMG NLQIDFADPS RADDARQLFA LSCTAEEQGV LPDDLSGVIR RLWADHGVQA CFGRSREYQL NDSAAYYLND L ERIAQSDY IPTQQDVLRT RVKTTGIVET HFTFKDLHFK MFDVGAQRSE RKKWIHCFEG VTAIIFCVAL SAYDLVLAED EE MNRMHAS MKLFDSICNN KWFTDTSIIL FLNKKDLFEE KITHSPLTIC FPEYTGANKY DEAASYIQSK FEDLNKRKDT KEI YTHFTC STDTKNVQFV FDAVTDVIIK NNLKDCGLF |
-Macromolecule #4: 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: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 38.744371 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI ...String: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CRQTFTGHES DI NAICFFP NGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDALKADRAG VLA GHDNRV SCLGVTDDGM AVATGSWDSF LKIWN |
-Macromolecule #5: 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: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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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 BIOQUANTUM (6k x 4k) / Average electron dose: 2.1875 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1094657 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |