8FJ2

Crystal Structure of the Tick Evasin EVA-AAM1001(C8) Complexed to Human Chemokine CCL17

8FJ2 の概要

• エントリーDOI: 10.2210/pdb8fj2/pdb
• 分子名称: Evasin P1243, C-C motif chemokine 17 (3 entities in total)
• 機能のキーワード: evasin, chemokine-binding protein, ticks, cytokine
• 由来する生物種: Amblyomma americanum (Lone Star tick); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 19366.80

構造登録者

Devkota, S.R.,Bhusal, R.P.,Aryal, P.,Wilce, M.C.J.,Stone, M.J. (登録日: 2022-12-19, 公開日: 2023-03-29, 最終更新日: 2024-10-30)

主引用文献

Devkota, S.R.,Aryal, P.,Pokhrel, R.,Jiao, W.,Perry, A.,Panjikar, S.,Payne, R.J.,Wilce, M.C.J.,Bhusal, R.P.,Stone, M.J.
Engineering broad-spectrum inhibitors of inflammatory chemokines from subclass A3 tick evasins.
Nat Commun, 14:4204-4204, 2023

PubMed Abstract: Chemokines are key regulators of leukocyte trafficking and attractive targets for anti-inflammatory therapy. Evasins are chemokine-binding proteins from tick saliva, whose application as anti-inflammatory therapeutics will require manipulation of their chemokine target selectivity. Here we describe subclass A3 evasins, which are unique to the tick genus Amblyomma and distinguished from "classical" class A1 evasins by an additional disulfide bond near the chemokine recognition interface. The A3 evasin EVA-AAM1001 (EVA-A) bound to CC chemokines and inhibited their receptor activation. Unlike A1 evasins, EVA-A was not highly dependent on N- and C-terminal regions to differentiate chemokine targets. Structures of chemokine-bound EVA-A revealed a deep hydrophobic pocket, unique to A3 evasins, that interacts with the residue immediately following the CC motif of the chemokine. Mutations to this pocket altered the chemokine selectivity of EVA-A. Thus, class A3 evasins provide a suitable platform for engineering proteins with applications in research, diagnosis or anti-inflammatory therapy.

PubMed: 37452046
DOI: 10.1038/s41467-023-39879-3

実験手法

X-RAY DIFFRACTION (2.07 Å)