+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35293 | |||||||||||||||
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Title | C3a-C3aR-Go (C3aR-Go complex only, Original Map) | |||||||||||||||
Map data | ||||||||||||||||
Sample |
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Keywords | GPCR / G protein / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
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_35293.map.gz | 168.1 MB | EMDB map data format | |
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Header (meta data) | emd-35293-v30.xml emd-35293.xml | 14.8 KB 14.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_35293_fsc.xml | 11.9 KB | Display | FSC data file |
Images | emd_35293.png | 40 KB | ||
Filedesc metadata | emd-35293.cif.gz | 4.2 KB | ||
Others | emd_35293_half_map_1.map.gz emd_35293_half_map_2.map.gz | 165 MB 165 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35293 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35293 | HTTPS FTP |
-Validation report
Summary document | emd_35293_validation.pdf.gz | 792.4 KB | Display | EMDB validaton report |
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Full document | emd_35293_full_validation.pdf.gz | 791.9 KB | Display | |
Data in XML | emd_35293_validation.xml.gz | 20.7 KB | Display | |
Data in CIF | emd_35293_validation.cif.gz | 26.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35293 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35293 | HTTPS FTP |
-Related structure data
Related structure data | 8hptC 8hqcC 8i95C 8i97C 8i9aC 8i9lC 8i9sC 8ia2C 8j6dC 8jzzC C: citing same article (ref.) |
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-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_35293.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
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: #1
File | emd_35293_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_35293_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : C3a-C3aR-Go (C3aR-Go complex only, Original Map)
Entire | Name: C3a-C3aR-Go (C3aR-Go complex only, Original Map) |
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Components |
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-Supramolecule #1: C3a-C3aR-Go (C3aR-Go complex only, Original Map)
Supramolecule | Name: C3a-C3aR-Go (C3aR-Go complex only, Original Map) / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: Homo sapiens (human) |
-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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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: 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 |