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TitleRevealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins.
Journal, issue, pagesNat Chem Biol, Vol. 19, Issue 11, Page 1351-1360, Year 2023
Publish dateMay 11, 2023
AuthorsYue Wang / Weiyi Liu / Youwei Xu / Xinheng He / Qingning Yuan / Ping Luo / Wenjia Fan / Jingpeng Zhu / Xinyue Zhang / Xi Cheng / Yi Jiang / H Eric Xu / Youwen Zhuang /
PubMed AbstractThe complement receptors C3aR and C5aR1, whose signaling is selectively activated by anaphylatoxins C3a and C5a, are important regulators of both innate and adaptive immune responses. Dysregulations ...The complement receptors C3aR and C5aR1, whose signaling is selectively activated by anaphylatoxins C3a and C5a, are important regulators of both innate and adaptive immune responses. Dysregulations of C3aR and C5aR1 signaling lead to multiple inflammatory disorders, including sepsis, asthma and acute respiratory distress syndrome. The mechanism underlying endogenous anaphylatoxin recognition and activation of C3aR and C5aR1 remains elusive. Here we reported the structures of C3a-bound C3aR and C5a-bound C5aR1 as well as an apo-C3aR structure. These structures, combined with mutagenesis analysis, reveal a conserved recognition pattern of anaphylatoxins to the complement receptors that is different from chemokine receptors, unique pocket topologies of C3aR and C5aR1 that mediate ligand selectivity, and a common mechanism of receptor activation. These results provide crucial insights into the molecular understanding of C3aR and C5aR1 signaling and structural templates for rational drug design for treating inflammation disorders.
External linksNat Chem Biol / PubMed:37169960
MethodsEM (single particle)
Resolution2.9 - 3.2 Å
Structure data

34842

8hk2

EMDB-34842, PDB-8hk2:
C3aR-Gi-C3a protein complex
Method: EM (single particle) / Resolution: 2.9 Å

34843

8hk3

EMDB-34843, PDB-8hk3:
C3aR-Gi-apo protein complex
Method: EM (single particle) / Resolution: 3.2 Å

34846

8hk5

EMDB-34846, PDB-8hk5:
C5aR1-Gi-C5a protein complex
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-CLR:
CHOLESTEROL / Cholesterol

ChemComp-PLM:
PALMITIC ACID / Palmitic acid

Source
  • homo sapiens (human)
  • rattus norvegicus (Norway rat)
  • bos taurus (cattle)
KeywordsMEMBRANE PROTEIN / GPCR / C3aR / C3a / complement / C5aR1 / C5a

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