[English] 日本語
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 | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of C5a bound human C5aR1 in complex with Go (Composite map) | |||||||||||||||
Map data | Full map | |||||||||||||||
Sample |
| |||||||||||||||
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 / complement receptor mediated signaling pathway ...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 / complement receptor mediated signaling pathway / Activation of C3 and C5 / corticotropin-releasing hormone receptor 1 binding / negative regulation of macrophage chemotaxis / vesicle docking involved in exocytosis / positive regulation of neutrophil chemotaxis / complement activation, alternative pathway / : / chemokine activity / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / endopeptidase inhibitor activity / positive regulation of macrophage chemotaxis / amyloid-beta clearance / positive regulation of vascular endothelial growth factor production / negative regulation of insulin secretion / cellular defense response / G protein-coupled serotonin receptor binding / muscle contraction / positive regulation of chemokine production / positive regulation of epithelial cell proliferation / astrocyte activation / neutrophil chemotaxis / Peptide ligand-binding receptors / complement activation, classical pathway / secretory granule membrane / Regulation of Complement cascade / mRNA transcription by RNA polymerase II / locomotory behavior / G protein-coupled receptor activity / microglial cell activation / 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 / cognition / 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 / 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 / GPER1 signaling / chemotaxis / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / apical part of cell / 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 / basolateral plasma membrane / G alpha (i) signalling events / cell body / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / killing of cells of another organism / cell population proliferation / positive regulation of ERK1 and ERK2 cascade 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
| |||||||||||||||
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 |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_35292.map.gz | 166.9 MB | EMDB map data format | |
---|---|---|---|---|
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 |
-Validation report
Summary document | emd_35292_validation.pdf.gz | 818 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_35292_full_validation.pdf.gz | 817.6 KB | Display | |
Data in XML | emd_35292_validation.xml.gz | 20.4 KB | Display | |
Data in CIF | emd_35292_validation.cif.gz | 26.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35292 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35292 | HTTPS FTP |
-Related structure data
Related structure data | 8ia2MC 8hptC 8hqcC 8i95C 8i97C 8i9aC 8i9lC 8i9sC 8j6dC 8jzzC C: citing same article (ref.) M: atomic model generated by this map |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
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) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Full map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.0631 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: Half map B
File | emd_35292_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map B | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half map A
File | emd_35292_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map A | ||||||||||||
Projections & Slices |
| ||||||||||||
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 |
---|---|
Processing | 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: 10151 / 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: 3.0 µm / Nominal defocus min: 0.8 µm |