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Yorodumi- EMDB-35292: Structure of C5a bound human C5aR1 in complex with Go (Composite map) -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35292 | |||||||||||||||
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Title | Structure of C5a bound human C5aR1 in complex with Go (Composite map) | |||||||||||||||
Map data | Full map | |||||||||||||||
Sample |
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Keywords | GPCR / G protein / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Function / homology | Function and homology information complement component C5a signaling pathway / presynapse organization / regulation of tau-protein kinase activity / complement component C5a receptor activity / response to peptidoglycan / Terminal pathway of complement / membrane attack complex / sensory perception of chemical stimulus / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding ...complement component C5a signaling pathway / presynapse organization / regulation of tau-protein kinase activity / complement component C5a receptor activity / response to peptidoglycan / Terminal pathway of complement / membrane attack complex / sensory perception of chemical stimulus / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / complement receptor mediated signaling pathway / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / positive regulation of neutrophil chemotaxis / complement activation, alternative pathway / chemokine activity / dopamine receptor signaling pathway / endopeptidase inhibitor activity / positive regulation of macrophage chemotaxis / amyloid-beta clearance / activation of phospholipase C activity / positive regulation of vascular endothelial growth factor production / G protein-coupled serotonin receptor binding / cellular defense response / complement activation, classical pathway / positive regulation of chemokine production / Peptide ligand-binding receptors / neutrophil chemotaxis / secretory granule membrane / muscle contraction / positive regulation of epithelial cell proliferation / Regulation of Complement cascade / astrocyte activation / G protein-coupled receptor activity / microglial cell activation / Olfactory Signaling Pathway / G-protein beta/gamma-subunit complex binding / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / mRNA transcription by RNA polymerase II / 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 / 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 / cognition / 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 / 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 / GPER1 signaling / G-protein beta-subunit binding / positive regulation of angiogenesis / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / chemotaxis / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / apical part of cell / GTPase binding / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / basolateral plasma membrane / killing of cells of another organism / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway / positive regulation of ERK1 and ERK2 cascade / defense response to Gram-positive bacterium / immune response / inflammatory response / G protein-coupled receptor signaling pathway Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.21 Å | |||||||||||||||
Authors | Yadav MK / Yadav R / Maharana J / 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_35292.map.gz | 166.9 MB | EMDB map data format | |
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Header (meta data) | emd-35292-v30.xml emd-35292.xml | 26.4 KB 26.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_35292_fsc.xml | 11.9 KB | Display | FSC data file |
Images | emd_35292.png | 37 KB | ||
Filedesc metadata | emd-35292.cif.gz | 7.2 KB | ||
Others | emd_35292_half_map_1.map.gz emd_35292_half_map_2.map.gz | 164.2 MB 164.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35292 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35292 | HTTPS FTP |
-Related structure data
Related structure data | 8ia2MC 8i95C 8i97C 8i9aC 8i9lC 8i9sC 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_35292.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Full map | ||||||||||||||||||||
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: Half map B
File | emd_35292_half_map_1.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_35292_half_map_2.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : C5a bound human C5aR1 in complex with Go
+Supramolecule #1: C5a bound human C5aR1 in complex with Go
+Supramolecule #2: C5a anaphylatoxin chemotactic receptor 1
+Supramolecule #3: C5a anaphylatoxin
+Supramolecule #4: Guanine nucleotide-binding protein G(o) subunit alpha
+Supramolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Supramolecule #6: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Supramolecule #7: Antibody fragment - ScFv16
+Macromolecule #1: C5a anaphylatoxin chemotactic receptor 1
+Macromolecule #2: C5a anaphylatoxin
+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 |
-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: 10151 / Average electron dose: 50.0 e/Å2 |