7B2D

Complement inhibitor CirpA1 from Rhipicephalus pulchellus

7B2D の概要

• エントリーDOI: 10.2210/pdb7b2d/pdb
• 関連するPDBエントリー: 7B26 7B28 7B29 7B2A
• 分子名称: CirpA1, D-MALATE (3 entities in total)
• 機能のキーワード: inhibitor, complement, tick, immunosuppressant
• 由来する生物種: Rhipicephalus pulchellus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20699.70

構造登録者

Lea, S.M.,Johnson, S.,Braunger, K. (登録日: 2020-11-26, 公開日: 2021-12-08, 最終更新日: 2024-11-20)

主引用文献

Braunger, K.,Ahn, J.,Jore, M.M.,Johnson, S.,Tang, T.T.L.,Pedersen, D.V.,Andersen, G.R.,Lea, S.M.
Structure and function of a family of tick-derived complement inhibitors targeting properdin.
Nat Commun, 13:317-317, 2022

PubMed Abstract: Activation of the serum-resident complement system begins a cascade that leads to activation of membrane-resident complement receptors on immune cells, thus coordinating serum and cellular immune responses. Whilst many molecules act to control inappropriate activation, Properdin is the only known positive regulator of the human complement system. By stabilising the alternative pathway C3 convertase it promotes complement self-amplification and persistent activation boosting the magnitude of the serum complement response by all triggers. In this work, we identify a family of tick-derived alternative pathway complement inhibitors, hereafter termed CirpA. Functional and structural characterisation reveals that members of the CirpA family directly bind to properdin, inhibiting its ability to promote complement activation, and leading to potent inhibition of the complement response in a species specific manner. We provide a full functional and structural characterisation of a properdin inhibitor, opening avenues for future therapeutic approaches.

PubMed: 35031611
DOI: 10.1038/s41467-021-27920-2

実験手法

X-RAY DIFFRACTION (1.96 Å)