8HK5

C5aR1-Gi-C5a protein complex

Summary for 8HK5

• Entry DOI: 10.2210/pdb8hk5/pdb
• EMDB information: 34842 34843 34846
• Descriptor: C5a anaphylatoxin chemotactic receptor 1, Complement C5, Guanine nucleotide-binding protein G(i) subunit alpha-1, ... (6 entities in total)
• Functional Keywords: gpcr, c5ar1, c5a, complement, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 133835.81

Authors

Wang, Y.,Liu, W.,Xu, Y.,Zhuang, Y.,Xu, H.E. (deposition date: 2022-11-24, release date: 2023-05-10, Last modification date: 2023-11-08)

Primary citation

Wang, Y.,Liu, W.,Xu, Y.,He, X.,Yuan, Q.,Luo, P.,Fan, W.,Zhu, J.,Zhang, X.,Cheng, X.,Jiang, Y.,Xu, H.E.,Zhuang, Y.
Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins.
Nat.Chem.Biol., 19:1351-1360, 2023

PubMed Abstract: 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.

PubMed: 37169960
DOI: 10.1038/s41589-023-01339-w

Experimental method

ELECTRON MICROSCOPY (3 Å)