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Open data
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Basic information
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Title | C5a-hC5aR1-Go complex (C5a only, Original map) | |||||||||||||||
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![]() | GPCR / G protein / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.88 Å | |||||||||||||||
![]() | Yadav MK / Yadav R / Maharana J / Banerjee R / Shukla AK / Gati C | |||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() 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. | |||||||||||||||
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Structure visualization
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Downloads & links
-EMDB archive
Map data | ![]() | 168 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.9 KB 13.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.9 KB | Display | ![]() |
Images | ![]() | 23.1 KB | ||
Filedesc metadata | ![]() | 4.1 KB | ||
Others | ![]() ![]() | 165 MB 164.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8hptC ![]() 8hqcC ![]() 8i95C ![]() 8i97C ![]() 8i9aC ![]() 8i9lC ![]() 8i9sC ![]() 8ia2C ![]() 8j6dC ![]() 8jzzC C: citing same article ( |
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Links
EMDB pages | ![]() ![]() |
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Map
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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_35296_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_35296_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : C5a-hC5aR1-Go complex (C5a only, Original map)
Entire | Name: C5a-hC5aR1-Go complex (C5a only, Original map) |
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Components |
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-Supramolecule #1: C5a-hC5aR1-Go complex (C5a only, Original map)
Supramolecule | Name: C5a-hC5aR1-Go complex (C5a only, Original map) / type: complex / ID: 1 / Parent: 0 |
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Source (natural) | Organism: ![]() |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Number real images: 10151 / 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 |