+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35275 | |||||||||||||||
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Title | Structure of C3a-C3aR-Go complex (Composite map) | |||||||||||||||
Map data | ||||||||||||||||
Sample |
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Keywords | GPCR / G protein / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Function / homology | Function and homology information complement component C3a receptor activity / complement component C5a receptor activity / oviduct epithelium development / C5L2 anaphylatoxin chemotactic receptor binding / regulation of triglyceride biosynthetic process / positive regulation of activation of membrane attack complex / vertebrate eye-specific patterning / positive regulation of apoptotic cell clearance / complement-mediated synapse pruning / Alternative complement activation ...complement component C3a receptor activity / complement component C5a receptor activity / oviduct epithelium development / C5L2 anaphylatoxin chemotactic receptor binding / regulation of triglyceride biosynthetic process / positive regulation of activation of membrane attack complex / vertebrate eye-specific patterning / positive regulation of apoptotic cell clearance / complement-mediated synapse pruning / Alternative complement activation / positive regulation of lipid storage / positive regulation of G protein-coupled receptor signaling pathway / mu-type opioid receptor binding / positive regulation of phagocytosis, engulfment / complement receptor mediated signaling pathway / corticotropin-releasing hormone receptor 1 binding / Activation of C3 and C5 / positive regulation of type IIa hypersensitivity / positive regulation of glucose transmembrane transport / complement-dependent cytotoxicity / positive regulation of neutrophil chemotaxis / complement activation, alternative pathway / complement activation / blood circulation / azurophil granule membrane / dopamine receptor signaling pathway / neuron remodeling / endopeptidase inhibitor activity / positive regulation of macrophage chemotaxis / amyloid-beta clearance / positive regulation of vascular endothelial growth factor production / G protein-coupled serotonin receptor binding / specific granule membrane / Purinergic signaling in leishmaniasis infection / complement activation, classical pathway / Peptide ligand-binding receptors / fatty acid metabolic process / muscle contraction / Regulation of Complement cascade / G protein-coupled receptor activity / calcium-mediated signaling / Post-translational protein phosphorylation / response to bacterium / 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-modulating G protein-coupled receptor signaling pathway / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / 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 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / 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 / positive regulation of receptor-mediated endocytosis / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / sensory perception of taste / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / positive regulation of angiogenesis / extracellular vesicle / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / G alpha (12/13) signalling events / chemotaxis / azurophil granule lumen / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / blood microparticle / secretory granule lumen Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.18 Å | |||||||||||||||
Authors | Yadav MK / Yadav R / Maharana J / Sarma P / Banerjee R / Shukla AK / Gati C | |||||||||||||||
Funding support | India, United Kingdom, 4 items
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Citation | Journal: Cell / Year: 2023 Title: Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors. Authors: Manish K Yadav / Jagannath Maharana / Ravi Yadav / Shirsha Saha / Parishmita Sarma / Chahat Soni / Vinay Singh / Sayantan Saha / Manisankar Ganguly / Xaria X Li / Samanwita Mohapatra / Sudha ...Authors: Manish K Yadav / Jagannath Maharana / Ravi Yadav / Shirsha Saha / Parishmita Sarma / Chahat Soni / Vinay Singh / Sayantan Saha / Manisankar Ganguly / Xaria X Li / Samanwita Mohapatra / Sudha Mishra / Htet A Khant / Mohamed Chami / Trent M Woodruff / Ramanuj Banerjee / Arun K Shukla / Cornelius Gati / Abstract: The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological ...The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological responses primarily via two GPCRs, C3aR and C5aR1. However, the molecular mechanism of ligand recognition, activation, and signaling bias of these receptors remains mostly elusive. Here, we present nine cryo-EM structures of C3aR and C5aR1 activated by their natural and synthetic agonists, which reveal distinct binding pocket topologies of complement anaphylatoxins and provide key insights into receptor activation and transducer coupling. We also uncover the structural basis of a naturally occurring mechanism to dampen the inflammatory response of C5a via proteolytic cleavage of the terminal arginine and the G-protein signaling bias elicited by a peptide agonist of C3aR identified here. In summary, our study elucidates the innerworkings of the complement anaphylatoxin receptors and should facilitate structure-guided drug discovery to target these receptors in a spectrum of disorders. | |||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_35275.map.gz | 166.1 MB | EMDB map data format | |
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Header (meta data) | emd-35275-v30.xml emd-35275.xml | 26.3 KB 26.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_35275_fsc.xml | 11.9 KB | Display | FSC data file |
Images | emd_35275.png | 32.2 KB | ||
Filedesc metadata | emd-35275.cif.gz | 7.2 KB | ||
Others | emd_35275_half_map_1.map.gz emd_35275_half_map_2.map.gz | 161.3 MB 162.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35275 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35275 | HTTPS FTP |
-Related structure data
Related structure data | 8i9lMC 8i95C 8i97C 8i9aC 8i9sC 8ia2C 8j6dC 8jzzC 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_35275.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.0631 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_35275_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35275_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Structure of C3a-C3aR-Go complex
+Supramolecule #1: Structure of C3a-C3aR-Go complex
+Supramolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Supramolecule #3: Guanine nucleotide-binding protein G(o) subunit alpha
+Supramolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Supramolecule #5: Antibody fragment - ScFv16
+Supramolecule #6: C3a anaphylatoxin chemotactic receptor
+Supramolecule #7: C3a Ligand
+Macromolecule #1: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #2: Guanine nucleotide-binding protein G(o) subunit alpha
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: Antibody fragment - ScFv16
+Macromolecule #5: C3a anaphylatoxin chemotactic receptor
+Macromolecule #6: C3a anaphylatoxin
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS GLACIOS |
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Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.8 µm |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Detector mode: COUNTING / Number real images: 20051 / Average electron dose: 50.0 e/Å2 |