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Yorodumi- EMDB-33633: Cryo-EM structure of C5a-bound C5aR1 in complex with Gi protein -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33633 | |||||||||
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Title | Cryo-EM structure of C5a-bound C5aR1 in complex with Gi protein | |||||||||
Map data | ||||||||||
Sample |
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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 / complement receptor mediated signaling pathway / Activation of C3 and C5 ...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 / 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 / endopeptidase inhibitor activity / positive regulation of macrophage chemotaxis / amyloid-beta clearance / positive regulation of vascular endothelial growth factor production / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / cellular defense response / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / positive regulation of chemokine production / positive regulation of epithelial cell proliferation / regulation of mitotic spindle organization / cellular response to forskolin / astrocyte activation / neutrophil chemotaxis / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / complement activation, classical pathway / secretory granule membrane / Regulation of Complement cascade / mRNA transcription by RNA polymerase II / Regulation of insulin secretion / G protein-coupled receptor binding / 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 / response to peptide hormone / 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 / GDP binding / 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 / cell cortex / basolateral plasma membrane / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | Feng YY / Zhao C / Yan W / Shao ZH | |||||||||
Funding support | China, 1 items
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Citation | Journal: Cell Res / Year: 2023 Title: Mechanism of activation and biased signaling in complement receptor C5aR1. Authors: Yuying Feng / Chang Zhao / Yue Deng / Heli Wang / Liang Ma / Sicen Liu / Xiaowen Tian / Bo Wang / Yan Bin / Peipei Chen / Wei Yan / Ping Fu / Zhenhua Shao / Abstract: The complement system plays an important role in the innate immune response to invading pathogens. The complement fragment C5a is one of its important effector components and exerts diverse ...The complement system plays an important role in the innate immune response to invading pathogens. The complement fragment C5a is one of its important effector components and exerts diverse physiological functions through activation of the C5a receptor 1 (C5aR1) and associated downstream G protein and β-arrestin signaling pathways. Dysfunction of the C5a-C5aR1 axis is linked to numerous inflammatory and immune-mediated diseases, but the structural basis for activation and biased signaling of C5aR1 remains elusive. Here, we present cryo-electron microscopy structures of the activated wild-type C5aR1-G protein complex bound to each of the following: C5a, the hexapeptidic agonist C5a, and the G protein-biased agonist BM213. The structures reveal the landscape of the C5a-C5aR1 interaction as well as a common motif for the recognition of diverse orthosteric ligands. Moreover, combined with mutagenesis studies and cell-based pharmacological assays, we deciphered a framework for biased signaling using different peptide analogs and provided insight into the activation mechanism of C5aR1 by solving the structure of C5aR1 mutant-G signaling activation complex induced by C089, which exerts antagonism on wild-type C5aR1. In addition, unusual conformational changes in the intracellular end of transmembrane domain 7 and helix 8 upon agonist binding suggest a differential signal transduction process. Collectively, our study provides mechanistic understanding into the ligand recognition, biased signaling modulation, activation, and G protein coupling of C5aR1, which may facilitate the future design of therapeutic agents. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33633.map.gz | 55.3 MB | EMDB map data format | |
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Header (meta data) | emd-33633-v30.xml emd-33633.xml | 21.2 KB 21.2 KB | Display Display | EMDB header |
Images | emd_33633.png | 34.6 KB | ||
Others | emd_33633_half_map_1.map.gz emd_33633_half_map_2.map.gz | 49.5 MB 49.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33633 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33633 | HTTPS FTP |
-Validation report
Summary document | emd_33633_validation.pdf.gz | 715.1 KB | Display | EMDB validaton report |
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Full document | emd_33633_full_validation.pdf.gz | 714.6 KB | Display | |
Data in XML | emd_33633_validation.xml.gz | 12.3 KB | Display | |
Data in CIF | emd_33633_validation.cif.gz | 14.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33633 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33633 | HTTPS FTP |
-Related structure data
Related structure data | 7y64MC 7y65C 7y66C 7y67C M: atomic model generated by this map C: citing same article (ref.) |
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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_33633.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.85 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_33633_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_33633_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : C5a-bound C5aR1 in complex with Gi heterotrimer
+Supramolecule #1: C5a-bound C5aR1 in complex with Gi heterotrimer
+Supramolecule #2: Gi heterotrimer
+Supramolecule #3: scFV16
+Supramolecule #4: C5a-bound C5aR1
+Macromolecule #1: Guanine nucleotide-binding protein G(i) subunit alpha-1
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: scFV16
+Macromolecule #5: C5a anaphylatoxin chemotactic receptor 1
+Macromolecule #6: C5a anaphylatoxin
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 66.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 623262 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |