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Open data
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Basic information
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| Title | Structure of EP54 bound mouse C3aR in complex with Go | ||||||||||||
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Keywords | GPCR / G protein / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
| Function / homology | Function and homology informationcomplement component C3a receptor activity / Peptide ligand-binding receptors / Regulation of Complement cascade / Muscarinic acetylcholine receptors / G protein-coupled acetylcholine receptor activity / G alpha (i) signalling events / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / vesicle docking involved in exocytosis ...complement component C3a receptor activity / Peptide ligand-binding receptors / Regulation of Complement cascade / Muscarinic acetylcholine receptors / G protein-coupled acetylcholine receptor activity / G alpha (i) signalling events / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / vesicle docking involved in exocytosis / positive regulation of neutrophil chemotaxis / G protein-coupled dopamine receptor signaling pathway / regulation of locomotion / positive regulation of macrophage chemotaxis / regulation of heart contraction / parallel fiber to Purkinje cell synapse / positive regulation of vascular endothelial growth factor production / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / postsynaptic modulation of chemical synaptic transmission / Neutrophil degranulation / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / muscle contraction / locomotory behavior / calcium-mediated signaling / negative regulation of insulin secretion / G protein-coupled receptor activity / GABA-ergic synapse / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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-coupled acetylcholine receptor signaling pathway / positive regulation of angiogenesis / chemotaxis / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / 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 / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / G protein activity / cell body / presynaptic membrane / GTPase binding / Ca2+ pathway / fibroblast proliferation / 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 / chemical synaptic transmission / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Ras protein signal transduction / postsynaptic membrane / cell surface receptor signaling pathway / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / dendrite / GTP binding / protein-containing complex binding / glutamatergic synapse / signal transduction / extracellular exosome Similarity search - Function | ||||||||||||
| Biological species | Homo sapiens (human) / ![]() | ||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.38 Å | ||||||||||||
Authors | Banerjee R / Yadav MK / Yadav R / Ganguly M / Mishra S / Dalal A / Gati C / Shukla AK | ||||||||||||
| Funding support | India, United Kingdom, 3 items
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Citation | Journal: bioRxiv / Year: 2025Title: Molecular fingerprints of a convergent mechanism orchestrating diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptors. Authors: Sudha Mishra / Manish K Yadav / Annu Dalal / Manisankar Ganguly / Ravi Yadav / Kazuhiro Sawada / Divyanshu Tiwari / Nabarun Roy / Nilanjana Banerjee / Jenny N Fung / Jianina Marallag / ...Authors: Sudha Mishra / Manish K Yadav / Annu Dalal / Manisankar Ganguly / Ravi Yadav / Kazuhiro Sawada / Divyanshu Tiwari / Nabarun Roy / Nilanjana Banerjee / Jenny N Fung / Jianina Marallag / Cedric S Cui / Xaria X Li / John D Lee / Calvin Aaron Dsouza / Shirsha Saha / Parishmita Sarma / Ganita Rawat / Houming Zhu / Htet A Khant / Richard J Clark / Fumiya K Sano / Ramanuj Banerjee / Trent M Woodruff / Osamu Nureki / Cornelius Gati / Arun K Shukla / ![]() Abstract: Complement anaphylatoxin receptors (C3aR and C5aR1) are prototypical G protein-coupled receptors (GPCRs) playing crucial physiological roles in innate immunity by combating pathogenic infections and ...Complement anaphylatoxin receptors (C3aR and C5aR1) are prototypical G protein-coupled receptors (GPCRs) playing crucial physiological roles in innate immunity by combating pathogenic infections and orchestrating inflammatory responses. They continue to be important therapeutic targets for multiple disorders including autoimmune diseases, acute and chronic inflammation, and allergy-related conditions. Recent structural coverage has provided important insights into their activation and signaling, however, confounding observations in the literature related to ligand efficacy and functional responses, especially in different model systems, present a major challenge for drug discovery efforts. Here, we systematically and comprehensively profile a broad set of natural and synthetic ligands at C3aR and C5aR1 and discover a previously unanticipated level of functional specialization in terms of species-specific pharmacology and receptor activation. Taking a lead from this, we determine seventeen cryo-EM structures of different ligand-receptor-G-protein complexes and uncover distinct orientation of agonists between the human and mouse receptors despite an overlapping positioning in the orthosteric binding pocket. Combined with extensive mutagenesis and functional assays, these structural snapshots allow us to decode and validate a convergent molecular mechanism involving a "Five-Point-Switch" in these receptors that orchestrates the recognition and efficacy of diverse agonists. We also identify species-specific differences at the level of phosphorylation patterns encoded in the carboxyl-terminus of these receptors and directly visualize their impact on βarr binding and activation using cryo-EM structures. Interestingly, we observe that βarrs engage with the mouse C5aR1 using a variation of previously discovered P-X-P-P phosphorylation motif via a "Sliding-Mechanism" and also exhibit distinct oligomeric state for the human vs. mouse receptors. Taken together, this study elucidates functional specialization at the complement anaphylatoxin receptors and underlying molecular mechanisms, offering a previously lacking framework with direct and immediate implications for the development of novel therapeutics. | ||||||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_64276.map.gz | 32.1 MB | EMDB map data format | |
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| Header (meta data) | emd-64276-v30.xml emd-64276.xml | 26.9 KB 26.9 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_64276_fsc.xml | 7.1 KB | Display | FSC data file |
| Images | emd_64276.png | 123.7 KB | ||
| Filedesc metadata | emd-64276.cif.gz | 7.5 KB | ||
| Others | emd_64276_half_map_1.map.gz emd_64276_half_map_2.map.gz | 35.7 MB 35.7 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-64276 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-64276 | HTTPS FTP |
-Validation report
| Summary document | emd_64276_validation.pdf.gz | 702 KB | Display | EMDB validaton report |
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| Full document | emd_64276_full_validation.pdf.gz | 701.5 KB | Display | |
| Data in XML | emd_64276_validation.xml.gz | 14.4 KB | Display | |
| Data in CIF | emd_64276_validation.cif.gz | 18.7 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-64276 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-64276 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9umjMC ![]() 9kugC ![]() 9kutC ![]() 9kv6C ![]() 9kv8C ![]() 9kvpC ![]() 9kwgC ![]() 9kwxC ![]() 9kx6C ![]() 9kxsC ![]() 9ky2C ![]() 9kyuC ![]() 9kz2C ![]() 9kz8C ![]() 9kzkC ![]() 9l0hC ![]() 9umrC ![]() 9umxC M: atomic model generated by this map C: citing same article ( |
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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_64276.map.gz / Format: CCP4 / Size: 38.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.5141 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: #1
| File | emd_64276_half_map_1.map | ||||||||||||
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-Half map: #2
| File | emd_64276_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
+Entire : EP54 bound to mouse C3aR in complex with Go
+Supramolecule #1: EP54 bound to mouse C3aR in complex with Go
+Supramolecule #2: EP54 ligand
+Supramolecule #3: Guanine nucleotide-binding protein G(o) subunit alpha
+Supramolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Supramolecule #5: C3a anaphylatoxin chemotactic receptor, C3aR (mouse)
+Supramolecule #6: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Supramolecule #7: Antibody fragment
+Macromolecule #1: EP54 Ligand
+Macromolecule #2: Muscarinic acetylcholine receptor M4,C3a anaphylatoxin chemotacti...
+Macromolecule #3: Guanine nucleotide-binding protein G(o) subunit alpha
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #6: Antibody fragment ScFv16
-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: 7.4 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS GLACIOS |
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| Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Detector mode: COUNTING / Average electron dose: 50.0 e/Å2 |
| Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.2 µm / Nominal defocus min: 0.8 µm |
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Image processing
-Atomic model buiding 1
| Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
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| Output model | ![]() PDB-9umj: |
Movie
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About Yorodumi




Keywords
Homo sapiens (human)
Authors
India,
United Kingdom, 3 items
Citation





































































Z (Sec.)
Y (Row.)
X (Col.)






































FIELD EMISSION GUN
