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Open data
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Basic information
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| Title | Structure of JR14a-C3aR-Gi-scFv16 complex | |||||||||
Map data | NU refine sharp map | |||||||||
Sample |
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Keywords | GPCR / MEMBRANE PROTEIN | |||||||||
| Function / homology | Function and homology informationcomplement component C3a receptor activity / complement component C5a receptor activity / complement receptor mediated signaling pathway / positive regulation of neutrophil chemotaxis / blood circulation / azurophil granule membrane / positive regulation of macrophage chemotaxis / positive regulation of vascular endothelial growth factor production / specific granule membrane / Purinergic signaling in leishmaniasis infection ...complement component C3a receptor activity / complement component C5a receptor activity / complement receptor mediated signaling pathway / positive regulation of neutrophil chemotaxis / blood circulation / azurophil granule membrane / positive regulation of macrophage chemotaxis / positive regulation of vascular endothelial growth factor production / specific granule membrane / Purinergic signaling in leishmaniasis infection / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / cellular response to forskolin / Peptide ligand-binding receptors / Regulation of Complement cascade / regulation of mitotic spindle organization / Regulation of insulin secretion / calcium-mediated signaling / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / G protein-coupled receptor activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / centriolar satellite / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / chemotaxis / positive regulation of angiogenesis / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / GDP binding / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / ADP signalling through P2Y purinoceptor 1 / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / G alpha (12/13) signalling events / extracellular vesicle / sensory perception of taste / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / positive regulation of cytosolic calcium ion concentration / G protein activity / retina development in camera-type eye / GTPase binding / Ca2+ pathway / fibroblast proliferation / midbody / cell cortex / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / ciliary basal body / G protein-coupled receptor signaling pathway / inflammatory response / lysosomal membrane / cell division / GTPase activity / synapse / Neutrophil degranulation Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.53 Å | |||||||||
Authors | Kim J / Ko S / Choi H-J | |||||||||
| Funding support | Korea, Republic Of, 1 items
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Citation | Journal: EMBO J / Year: 2025Title: Structural insights into small-molecule agonist recognition and activation of complement receptor C3aR. Authors: Jinuk Kim / Saebom Ko / Chulwon Choi / Jungnam Bae / Hyeonsung Byeon / Chaok Seok / Hee-Jung Choi / ![]() Abstract: The complement system plays crucial roles in innate immunity and inflammatory responses. The anaphylatoxin C3a mediates pro-inflammatory and chemotactic functions through the G protein-coupled ...The complement system plays crucial roles in innate immunity and inflammatory responses. The anaphylatoxin C3a mediates pro-inflammatory and chemotactic functions through the G protein-coupled receptor C3aR. While the active structure of the C3a-C3aR-G complex has been determined, the inactive conformation and activation mechanism of C3aR remain elusive. Here we report the cryo-EM structure of ligand-free, G protein-free C3aR, providing insights into its inactive conformation. In addition, we determine the structures of C3aR in complex with the synthetic small-molecule agonist JR14a in two distinct conformational states: a G protein-free intermediate, and a fully active G-bound state. The structure of the active JR14a-bound C3aR reveals that JR14a engages in highly conserved interactions with C3aR, similar to the binding of the C-terminal pentapeptide of C3a, along with JR14a-specific interactions. Structural comparison of C3aR in the apo, intermediate, and fully active states provides novel insights into the conformational landscape and activation mechanism of C3aR and defines a molecular basis explaining its high basal activity. Our results may aid in the rational design of therapeutics targeting complement-related inflammatory disorders. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_60782.map.gz | 230.1 MB | EMDB map data format | |
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| Header (meta data) | emd-60782-v30.xml emd-60782.xml | 26.1 KB 26.1 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_60782_fsc.xml | 13.2 KB | Display | FSC data file |
| Images | emd_60782.png | 63.3 KB | ||
| Filedesc metadata | emd-60782.cif.gz | 7.3 KB | ||
| Others | emd_60782_additional_1.map.gz emd_60782_half_map_1.map.gz emd_60782_half_map_2.map.gz | 228.2 MB 226.8 MB 226.8 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-60782 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-60782 | HTTPS FTP |
-Validation report
| Summary document | emd_60782_validation.pdf.gz | 838.9 KB | Display | EMDB validaton report |
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| Full document | emd_60782_full_validation.pdf.gz | 838.4 KB | Display | |
| Data in XML | emd_60782_validation.xml.gz | 21.9 KB | Display | |
| Data in CIF | emd_60782_validation.cif.gz | 28.6 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-60782 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-60782 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9ipvMC ![]() 9ipyC ![]() 9isiC C: citing same article ( M: atomic model generated by this map |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_60782.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | NU refine sharp map | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.81 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Additional map: vop max of the C3aR focused map and...
| File | emd_60782_additional_1.map | ||||||||||||
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| Annotation | vop max of the C3aR focused map and Gi complex focused map EMD-60784 (C3aR focused) EMD-60783 (G protein focused) | ||||||||||||
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| Density Histograms |
-Half map: half map
| File | emd_60782_half_map_1.map | ||||||||||||
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| Annotation | half map | ||||||||||||
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| Density Histograms |
-Half map: half map
| File | emd_60782_half_map_2.map | ||||||||||||
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| Annotation | half map | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : C3aR-Gi complex
| Entire | Name: C3aR-Gi complex |
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| Components |
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-Supramolecule #1: C3aR-Gi complex
| Supramolecule | Name: C3aR-Gi complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 140 kDa/nm |
-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: 40.415031 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGGQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF 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 Details: GPGSSGS : HRV 3C protease site (LEVLFQ / GP) + N-terminal linker (GSSGS) Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 37.728152 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: GPGSSGSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD ...String: GPGSSGSELD 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: 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: 3 / 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: ![]() |
| Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #4: C3a anaphylatoxin chemotactic receptor
| Macromolecule | Name: C3a anaphylatoxin chemotactic receptor / type: protein_or_peptide / ID: 4 Details: DYKDDDDASID : Expression tag ASLEVLF (483-490) : remaining HRV-3C Protease site Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 56.049109 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: DYKDDDDASI DMASFSAETN STDLLSQPWN EPPVILSMVI LSLTFLLGLP GNGLVLWVAG LKMQRTVNTI WFLHLTLADL LCCLSLPFS LAHLALQGQW PYGRFLCKLI PSIIVLNMFA SVFLLTAISL DRCLVVFKPI WCQNHRNVGM ACSICGCIWV V AFVMCIPV ...String: DYKDDDDASI DMASFSAETN STDLLSQPWN EPPVILSMVI LSLTFLLGLP GNGLVLWVAG LKMQRTVNTI WFLHLTLADL LCCLSLPFS LAHLALQGQW PYGRFLCKLI PSIIVLNMFA SVFLLTAISL DRCLVVFKPI WCQNHRNVGM ACSICGCIWV V AFVMCIPV FVYREIFTTD NHNRCGYKFG LSSSLDYPDF YGDPLENRSL ENIVQPPGEM NDRLDPSSFQ TNDHPWTVPT VF QPQTFQR PSADSLPRGS ARLTSQNLYS NVFKPADVVS PKIPSGFPIE DHETSPLDNS DAFLSTHLKL FPSASSNSFY ESE LPQGFQ DYYNLGQFTD DDQVPTPLVA ITITRLVVGF LLPSVIMIAC YSFIVFRMQR GRFAKSQSKT FRVAVVVVAV FLVC WTPYH IFGVLSLLTD PETPLGKTLM SWDHVCIALA SANSCFNPFL YALLGKDFRK KARQSIQGIL EAAFSEELTR STHCP SNNV ISERNSTTVA SLEVLFQ UniProtKB: C3a anaphylatoxin chemotactic receptor |
-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: Homo sapiens (human) |
| Molecular weight | Theoretical: 27.784896 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAAHHHHHH HH |
-Macromolecule #6: (2~{S})-5-[bis(azanyl)methylideneamino]-2-[[5-[bis(4-chlorophenyl...
| Macromolecule | Name: (2~{S})-5-[bis(azanyl)methylideneamino]-2-[[5-[bis(4-chlorophenyl)methyl]-3-methyl-thiophen-2-yl]carbonylamino]pentanoic acid type: ligand / ID: 6 / Number of copies: 1 / Formula: A1D9A |
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| Molecular weight | Theoretical: 533.47 Da |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 8 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 60.0 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: 2.0 µm / Nominal defocus min: 0.9 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi




Keywords
Homo sapiens (human)
Authors
Korea, Republic Of, 1 items
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Processing
FIELD EMISSION GUN

