+
Open data
-
Basic information
| Entry | ![]() | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Title | C5a bound C5aR1 in complex with beta-arrestin1 | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | C5aR2 / GPCR / membrane protein / active / arrestin / C5a-desArg / MEMBRANE PROTEIN/IMMUNE SYSTEM / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | |||||||||
| Function / homology | Function and homology informationTGFBR3 regulates TGF-beta signaling / presynapse organization / complement component C5a signaling pathway / MAP2K and MAPK activation / Activation of SMO / Golgi Associated Vesicle Biogenesis / Lysosome Vesicle Biogenesis / Terminal pathway of complement / membrane attack complex / complement component C5a receptor activity ...TGFBR3 regulates TGF-beta signaling / presynapse organization / complement component C5a signaling pathway / MAP2K and MAPK activation / Activation of SMO / Golgi Associated Vesicle Biogenesis / Lysosome Vesicle Biogenesis / Terminal pathway of complement / membrane attack complex / complement component C5a receptor activity / AP-2 adaptor complex binding / Ub-specific processing proteases / clathrin coat of coated pit / Cargo recognition for clathrin-mediated endocytosis / clathrin heavy chain binding / Activation of C3 and C5 / Clathrin-mediated endocytosis / negative regulation of macrophage chemotaxis / sensory perception of chemical stimulus / complement activation, GZMK pathway / other organism cell membrane / clathrin-dependent endocytosis / desensitization of G protein-coupled receptor signaling pathway / acetylcholine receptor binding / complement receptor mediated signaling pathway / complement activation, alternative pathway / G protein-coupled receptor internalization / positive regulation of neutrophil chemotaxis / inositol hexakisphosphate binding / chemokine activity / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (s) signalling events / clathrin binding / sensory perception / endopeptidase inhibitor activity / positive regulation of macrophage chemotaxis / small molecule binding / pseudopodium / phosphatidylinositol-3,4,5-trisphosphate binding / amyloid-beta clearance / negative regulation of Notch signaling pathway / positive regulation of receptor internalization / complement activation, classical pathway / positive regulation of vascular endothelial growth factor production / cellular defense response / positive regulation of chemokine production / astrocyte activation / positive regulation of epithelial cell proliferation / Regulation of Complement cascade / secretory granule membrane / Peptide ligand-binding receptors / microglial cell activation / receptor internalization / positive regulation of protein phosphorylation / mRNA transcription by RNA polymerase II / G protein-coupled receptor binding / cognition / chemotaxis / G protein-coupled receptor activity / positive regulation of angiogenesis / apical part of cell / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / protein transport / positive regulation of cytosolic calcium ion concentration / cytoplasmic vesicle / killing of cells of another organism / G alpha (i) signalling events / molecular adaptor activity / basolateral plasma membrane / ubiquitin-dependent protein catabolic process / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / immune response / inflammatory response / G protein-coupled receptor signaling pathway / signaling receptor binding / Neutrophil degranulation / signal transduction / DNA-templated transcription / : / extracellular exosome / extracellular region / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / ![]() ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Qin J / Cai C / Shan M / Zhang Y | |||||||||
| Funding support | 1 items
| |||||||||
Citation | Journal: Cell Res / Year: 2026Title: Atypical signaling, ligand recognition and selective agonist discovery of complement receptor C5aR2. Authors: Jiao Qin / Chenxi Cai / Mayu Shan / Suqing Zhou / Qingya Shen / Tianyi Zhu / Mingming Zhao / Yang Mei / Fanghan Ji / Dan-Dan Shen / Shao-Kun Zang / Huibing Zhang / Haomang Xu / Ming Yang / ...Authors: Jiao Qin / Chenxi Cai / Mayu Shan / Suqing Zhou / Qingya Shen / Tianyi Zhu / Mingming Zhao / Yang Mei / Fanghan Ji / Dan-Dan Shen / Shao-Kun Zang / Huibing Zhang / Haomang Xu / Ming Yang / Wei-Wei Wang / Rong Xiao / Bing Yang / Chunyou Mao / Zhenhua Shao / Haijing Wu / Qianjin Lu / Yan Zhang / ![]() Abstract: C5a, the most potent anaphylatoxin in the complement system, exerts its effects through the canonical G protein-coupled receptor C5aR1 and the arrestin-coupled receptor C5aR2. Despite the critical ...C5a, the most potent anaphylatoxin in the complement system, exerts its effects through the canonical G protein-coupled receptor C5aR1 and the arrestin-coupled receptor C5aR2. Despite the critical role of C5aR2 in immunomodulation, the molecular mechanisms underlying its biased signaling, ligand recognition, and associated pathophysiology remain poorly understood. Here, we report cryo-electron microscopy structures of β-arrestin 1-bound C5aR2 and C5aR1 stimulated by C5a or its metabolite C5a. By combining structural analysis with functional assays, we identified the key structural determinants that prevent G protein coupling and confer intrinsic bias toward β-arrestins. Comparative analysis elucidated the distinct ligand recognition mechanism of C5aR2 and explained the retained affinity of C5a for C5aR2. These findings guided the rational design of ZQ105, a highly selective C5aR2 agonist. Leveraging ZQ105 as a chemical probe, functional studies revealed that selective C5aR2 activation induces distinct pro-inflammatory responses and receptor internalization in neutrophils. This study provides novel structural insights into transducer engagement and ligand recognition by C5aR2, yielding a valuable pharmacological tool for exploring C5aR2-related pathophysiological processes. | |||||||||
| History |
|
-
Structure visualization
| Supplemental images |
|---|
-
Downloads & links
-EMDB archive
| Header (meta data) | emd-68263-v30.xml emd-68263.xml | 20.7 KB 20.7 KB | Display Display | EMDB header |
|---|---|---|---|---|
| Images | emd_68263.png | 44.5 KB | ||
| Map data | emd_68263.map.gz | 76.4 MB | EMDB map data format | |
| Filedesc metadata | emd-68263.cif.gz | 6.5 KB | ||
| Others | emd_68263_half_map_1.map.gz emd_68263_half_map_2.map.gz | 98.3 MB 98.4 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-68263 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-68263 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 22glMC ![]() 68177 ![]() 68262 ![]() 68264 ![]() 68516 ![]() 68517 ![]() 68520 ![]() 68524 ![]() 68525 ![]() 68529 ![]() 68531 ![]() 68534 ![]() 77405 ![]() 22crC ![]() 22gkC ![]() 22gmC M: atomic model generated by this map C: citing same article ( |
|---|---|
| Similar structure data | Similarity search - Function & homology F&H Search |
-
Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
|---|---|
| Related items in Molecule of the Month |
-
Map
-Supplemental data
-Half map: #2
| File | emd_68263_half_map_1.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-Half map: #1
| File | emd_68263_half_map_2.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-
Sample components
-Entire : C5a anaphylatoxin chemotactic receptor 1
| Entire | Name: C5a anaphylatoxin chemotactic receptor 1 |
|---|---|
| Components |
|
-Supramolecule #1: C5a anaphylatoxin chemotactic receptor 1
| Supramolecule | Name: C5a anaphylatoxin chemotactic receptor 1 / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: C5a anaphylatoxin
| Macromolecule | Name: C5a anaphylatoxin / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 3.024564 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: IKAFTECCVV ASQLRANISH KDMQLGR UniProtKB: Complement C5 |
-Macromolecule #2: C5a anaphylatoxin chemotactic receptor 1
| Macromolecule | Name: C5a anaphylatoxin chemotactic receptor 1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 35.130289 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: RVPDILALVI FAVVFLVGVL GNALVVWVTA FEAKRTINAI WFLNLAVADF LSCLALPILF TSIVQHHHWP FGGAACSILP SLILLNMYA SILLLATISA DRFLLVFKPI WCQNFRGAGL AWIACAVAWG LALLLTIPSF LYRVVREEYF PPKVLCGVDY S HDKRRERA ...String: RVPDILALVI FAVVFLVGVL GNALVVWVTA FEAKRTINAI WFLNLAVADF LSCLALPILF TSIVQHHHWP FGGAACSILP SLILLNMYA SILLLATISA DRFLLVFKPI WCQNFRGAGL AWIACAVAWG LALLLTIPSF LYRVVREEYF PPKVLCGVDY S HDKRRERA VAIVRLVLGF LWPLLTLTIC YTFILLRTWS RRATRSTKTL KVVVAVVASF FIFWLPYQVT GIMMSFLEPS SP TFLLLKK LDSLCVSFAY INCCINPIIY VVAGQGFQGR LRKSLPSLLR NVLTEESVVR ESK(SEP)F(TPO)R(SEP) (TPO) VD(TPO) UniProtKB: C5a anaphylatoxin chemotactic receptor 1 |
-Macromolecule #3: Fab30 heavy chain
| Macromolecule | Name: Fab30 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 24.40718 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NVYSSSIHWV RQAPGKGLEW VASISSYYGY TYYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARSRQFWYSG LDYWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA ...String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NVYSSSIHWV RQAPGKGLEW VASISSYYGY TYYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARSRQFWYSG LDYWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEPKSCDK T |
-Macromolecule #4: Fab30 light chain
| Macromolecule | Name: Fab30 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 23.435064 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQYKYVPVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQYKYVPVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Macromolecule #5: Beta-arrestin-1
| Macromolecule | Name: Beta-arrestin-1 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 38.980805 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: TRVFKKASPN GKLTVYLGKR DFVDHIDLVE PVDGVVLVDP EYLKERRVYV TLTCAFRYGR EDLDVLGLTF RKDLFVANVQ SFPPAPEDK KPLTRLQERL IKKLGEHAYP FTFEIPPNLP CSVTLQPGPE DTGKACGVDY EVKAFCAENL EEKIHKRNSV R LVIEKVQY ...String: TRVFKKASPN GKLTVYLGKR DFVDHIDLVE PVDGVVLVDP EYLKERRVYV TLTCAFRYGR EDLDVLGLTF RKDLFVANVQ SFPPAPEDK KPLTRLQERL IKKLGEHAYP FTFEIPPNLP CSVTLQPGPE DTGKACGVDY EVKAFCAENL EEKIHKRNSV R LVIEKVQY APERPGPQPT AETTRQFLMS DKPLHLEASL DKEIYYHGEP ISVNVHVTNN TNKTVKKIKI SVRQYADICL FN TAQYKCP VAMEEADDTV APSSTFCKVY TLTPFLANNR EKRGLALDGK LKHEDTNLAS STLLREGANR EILGIIVSYK VKV KLVVSR GGLLGDLASS DVAVELPFTL M UniProtKB: Beta-arrestin-1 |
-Experimental details
-Structure determination
| Method | cryo EM |
|---|---|
Processing | single particle reconstruction |
| Aggregation state | particle |
-
Sample preparation
| Buffer | pH: 7.5 |
|---|---|
| Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
| Microscope | TFS KRIOS |
|---|---|
| Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 52.0 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: 1.5 µm / Nominal defocus min: 0.7000000000000001 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
Movie
Controller
About Yorodumi




Keywords
Homo sapiens (human)
Authors
Citation


















Z (Sec.)
Y (Row.)
X (Col.)







































Processing
FIELD EMISSION GUN
