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8HPT

Structure of C5a-pep bound mouse C5aR1 in complex with Go

8HPT の概要
エントリーDOI10.2210/pdb8hpt/pdb
EMDBエントリー34943
分子名称C5a anaphylatoxin chemotactic receptor 1, MEA-LYS-PRO-ZAL-ALC-DAR, Guanine nucleotide-binding protein G(o) subunit alpha, ... (6 entities in total)
機能のキーワードgpcr, g protein, signaling protein, signatling protein-immune system complex, signatling protein/immune system
由来する生物種Mus musculus (house mouse)
詳細
タンパク質・核酸の鎖数6
化学式量合計143551.60
構造登録者
Saha, S.,Maharana, J.,Yadav, M.K.,Sarma, P.,Chami, M.,Banerjee, R.,Shukla, A.K. (登録日: 2022-12-13, 公開日: 2023-10-18, 最終更新日: 2024-07-17)
主引用文献Yadav, M.K.,Maharana, J.,Yadav, R.,Saha, S.,Sarma, P.,Soni, C.,Singh, V.,Saha, S.,Ganguly, M.,Li, X.X.,Mohapatra, S.,Mishra, S.,Khant, H.A.,Chami, M.,Woodruff, T.M.,Banerjee, R.,Shukla, A.K.,Gati, C.
Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors.
Cell, 186:4956-4973.e21, 2023
Cited by
PubMed 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 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.
PubMed: 37852260
DOI: 10.1016/j.cell.2023.09.020
主引用文献が同じPDBエントリー
実験手法
ELECTRON MICROSCOPY (3.39 Å)
構造検証レポート
Validation report summary of 8hpt
検証レポート(詳細版)ダウンロードをダウンロード

238582

件を2025-07-09に公開中

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