+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-34843 | |||||||||
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Title | C3aR-Gi-apo protein complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | GPCR / C3aR / complement / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information complement component C3a receptor activity / complement component C5a receptor activity / 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 ...complement component C3a receptor activity / complement component C5a receptor activity / 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 / Ca2+ pathway / Activation of G protein gated Potassium channels / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / 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 / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / positive regulation of neutrophil chemotaxis / G alpha (i) signalling events / blood circulation / Thrombin signalling through proteinase activated receptors (PARs) / 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 / alkylglycerophosphoethanolamine phosphodiesterase activity / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / 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 / photoreceptor outer segment membrane / azurophil granule membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of macrophage chemotaxis / photoreceptor outer segment / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / positive regulation of vascular endothelial growth factor production / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / specific granule membrane / Purinergic signaling in leishmaniasis infection / 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 / Peptide ligand-binding receptors / Regulation of insulin secretion / G protein-coupled receptor binding / Regulation of Complement cascade / G protein-coupled receptor activity / calcium-mediated signaling / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / response to peptide hormone / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / GDP binding / heterotrimeric G-protein complex / positive regulation of angiogenesis / chemotaxis / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / cell body / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / midbody Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Rattus norvegicus (Norway rat) / Bos taurus (cattle) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Wang Y / Liu W / Xu Y / Zhuang Y / Xu HE | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Chem Biol / Year: 2023 Title: Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins. Authors: Yue Wang / Weiyi Liu / Youwei Xu / Xinheng He / Qingning Yuan / Ping Luo / Wenjia Fan / Jingpeng Zhu / Xinyue Zhang / Xi Cheng / Yi Jiang / H Eric Xu / Youwen Zhuang / Abstract: The complement receptors C3aR and C5aR1, whose signaling is selectively activated by anaphylatoxins C3a and C5a, are important regulators of both innate and adaptive immune responses. Dysregulations ...The complement receptors C3aR and C5aR1, whose signaling is selectively activated by anaphylatoxins C3a and C5a, are important regulators of both innate and adaptive immune responses. Dysregulations of C3aR and C5aR1 signaling lead to multiple inflammatory disorders, including sepsis, asthma and acute respiratory distress syndrome. The mechanism underlying endogenous anaphylatoxin recognition and activation of C3aR and C5aR1 remains elusive. Here we reported the structures of C3a-bound C3aR and C5a-bound C5aR1 as well as an apo-C3aR structure. These structures, combined with mutagenesis analysis, reveal a conserved recognition pattern of anaphylatoxins to the complement receptors that is different from chemokine receptors, unique pocket topologies of C3aR and C5aR1 that mediate ligand selectivity, and a common mechanism of receptor activation. These results provide crucial insights into the molecular understanding of C3aR and C5aR1 signaling and structural templates for rational drug design for treating inflammation disorders. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_34843.map.gz | 27.2 MB | EMDB map data format | |
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Header (meta data) | emd-34843-v30.xml emd-34843.xml | 19.6 KB 19.6 KB | Display Display | EMDB header |
Images | emd_34843.png | 28 KB | ||
Filedesc metadata | emd-34843.cif.gz | 6.5 KB | ||
Others | emd_34843_half_map_1.map.gz emd_34843_half_map_2.map.gz | 23.4 MB 23.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-34843 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34843 | HTTPS FTP |
-Related structure data
Related structure data | 8hk3MC 8hk2C 8hk5C C: citing same article (ref.) M: atomic model generated by this map |
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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_34843.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_34843_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_34843_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : C3aR-Gi-apo protein complex
Entire | Name: C3aR-Gi-apo protein complex |
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Components |
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-Supramolecule #1: C3aR-Gi-apo protein complex
Supramolecule | Name: C3aR-Gi-apo protein complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 160 KDa |
-Macromolecule #1: 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: 1 / 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 frugiperda (fall armyworm) |
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 UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-Macromolecule #2: 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: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 37.915496 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD ...String: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD TTCALWDIET GQQTTTFTGH TGDVMSLSLA PDTRLFVSGA CDASAKLWDV REGMCRQTFT GHESDINAIC FF PNGNAFA TGSDDATCRL FDLRADQELM TYSHDNIICG ITSVSFSKSG RLLLAGYDDF NCNVWDALKA DRAGVLAGHD NRV SCLGVT DDGMAVATGS WDSFLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #3: C3a anaphylatoxin chemotactic receptor
Macromolecule | Name: C3a anaphylatoxin chemotactic receptor / 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: 53.247195 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASFSAETNS TDLLSQPWNE PPVILSMVIL SLTFLLGLPG NGLVLWVAGL KMQRTVNTIW FLHLTLADLL CCLSLPFSLA HLALQGQWP YGRFLCKLIP SIIVLNMFAS VFLLTAISLD RCLVVFKPIW CQNHRNVGMA CSICGCIWVV AFVMCIPVFV Y REIFTTDN ...String: MASFSAETNS TDLLSQPWNE PPVILSMVIL SLTFLLGLPG NGLVLWVAGL KMQRTVNTIW FLHLTLADLL CCLSLPFSLA HLALQGQWP YGRFLCKLIP SIIVLNMFAS VFLLTAISLD RCLVVFKPIW CQNHRNVGMA CSICGCIWVV AFVMCIPVFV Y REIFTTDN HNRCGYKFGL SSSLDYPDFY GDPLENRSLE NIVQPPGEMN DRLDPSSFQT NDHPWTVPTV FQPQTFQRPS AD SLPRGSA RLTSQNLYSN VFKPADVVSP KIPSGFPIED HETSPLDNSD AFLSTHLKLF PSASSNSFYE SELPQGFQDY YNL GQFTDD DQVPTPLVAI TITRLVVGFL LPSVIMIACY SFIVFRMQRG RFAKSQSKTF RVAVVVVAVF LVCWTPYHIF GVLS LLTDP ETPLGKTLMS WDHVCIALAS ANSCFNPFLY ALLGKDFRKK ARQSIQGILE AAFSEELTRS THCPSNNVIS E UniProtKB: C3a anaphylatoxin chemotactic receptor |
-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 frugiperda (fall armyworm) |
Sequence | String: ASNNTASIAQ ARKLVEQLKM EANIDRIKVS KAAADLMAYC EAHAKEDPLL TPVPASENPF REKKFFC UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-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 norvegicus (Norway rat) |
Molecular weight | Theoretical: 26.277299 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS AGGGGSGGGG SGGGGSADIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS AGGGGSGGGG SGGGGSADIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL |
-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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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.2 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Particle selection | Number selected: 4404753 |
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Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 275847 |