8HK2

C3aR-Gi-C3a protein complex

8HK2 の概要

• エントリーDOI: 10.2210/pdb8hk2/pdb
• EMDBエントリー: 34842 34843 34846
• 分子名称: C3a anaphylatoxin chemotactic receptor, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (8 entities in total)
• 機能のキーワード: gpcr, c3ar, c3a, complement, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 176747.26

構造登録者

Wang, Y.,Liu, W.,Xu, Y.,Zhuang, Y.,Xu, H.E. (登録日: 2022-11-24, 公開日: 2023-05-10, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.9 Å)