+
Open data
-
Basic information
Entry | ![]() | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of C3a-C3aR-Go complex (Composite map) | |||||||||||||||
![]() | ||||||||||||||||
![]() |
| |||||||||||||||
![]() | GPCR / G protein / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Function / homology | ![]() 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 / mu-type opioid receptor binding / positive regulation of phagocytosis, engulfment / positive regulation of G protein-coupled receptor signaling pathway / complement receptor mediated signaling pathway / Activation of C3 and C5 / corticotropin-releasing hormone receptor 1 binding / positive regulation of type IIa hypersensitivity / positive regulation of glucose transmembrane transport / complement-dependent cytotoxicity / vesicle docking involved in exocytosis / positive regulation of neutrophil chemotaxis / complement activation, alternative pathway / blood circulation / complement activation / azurophil granule membrane / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / endopeptidase inhibitor activity / neuron remodeling / positive regulation of macrophage chemotaxis / amyloid-beta clearance / positive regulation of vascular endothelial growth factor production / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / Purinergic signaling in leishmaniasis infection / specific granule membrane / muscle contraction / fatty acid metabolic process / Peptide ligand-binding receptors / complement activation, classical pathway / Regulation of Complement cascade / locomotory behavior / G protein-coupled receptor activity / Post-translational protein phosphorylation / response to bacterium / calcium-mediated signaling / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / 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 / positive regulation of receptor-mediated endocytosis / 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 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / positive regulation of angiogenesis / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / GPER1 signaling / chemotaxis / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / azurophil granule lumen / 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 / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / cell body Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.18 Å | |||||||||||||||
![]() | Yadav MK / Yadav R / Maharana J / Sarma P / Banerjee R / Shukla AK / Gati C | |||||||||||||||
Funding support | ![]() ![]()
| |||||||||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 166.1 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 26.3 KB 26.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.9 KB | Display | ![]() |
Images | ![]() | 32.2 KB | ||
Filedesc metadata | ![]() | 7.2 KB | ||
Others | ![]() ![]() | 161.3 MB 162.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8i9lMC ![]() 8hptC ![]() 8hqcC ![]() 8i95C ![]() 8i97C ![]() 8i9aC ![]() 8i9sC ![]() 8ia2C ![]() 8j6dC ![]() 8jzzC C: citing same article ( M: atomic model generated by this map |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.0631 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #2
File | emd_35275_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_35275_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
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 |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | TFS GLACIOS |
---|---|
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 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.8 µm |