6STC

Crystal structure of the tick chemokine-binding protein Evasin-4 (SG 2)

6STC の概要

• エントリーDOI: 10.2210/pdb6stc/pdb
• 関連するPDBエントリー: 6ST4
• 分子名称: Evasin-4, ACETATE ION, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• 機能のキーワード: chemokine-binding protein, ticks, immune system
• 由来する生物種: Rhipicephalus sanguineus (Brown dog tick)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11811.81

構造登録者

Ramirez-Escudero, M.,Janssen, B.J.C. (登録日: 2019-09-10, 公開日: 2020-09-02, 最終更新日: 2024-11-20)

主引用文献

Denisov, S.S.,Ramirez-Escudero, M.,Heinzmann, A.C.A.,Ippel, J.H.,Dawson, P.E.,Koenen, R.R.,Hackeng, T.M.,Janssen, B.J.C.,Dijkgraaf, I.
Structural characterization of anti-CCL5 activity of the tick salivary protein evasin-4.
J.Biol.Chem., 295:14367-14378, 2020

PubMed Abstract: Ticks, as blood-sucking parasites, have developed a complex strategy to evade and suppress host immune responses during feeding. The crucial part of this strategy is expression of a broad family of salivary proteins, called Evasins, to neutralize chemokines responsible for cell trafficking and recruitment. However, structural information about Evasins is still scarce, and little is known about the structural determinants of their binding mechanism to chemokines. Here, we studied the structurally uncharacterized Evasin-4, which neutralizes a broad range of CC-motif chemokines, including the chemokine CC-motif ligand 5 (CCL5) involved in atherogenesis. Crystal structures of Evasin-4 and E66S CCL5, an obligatory dimeric variant of CCL5, were determined to a resolution of 1.3-1.8 Å. The Evasin-4 crystal structure revealed an L-shaped architecture formed by an N- and C-terminal subdomain consisting of eight β-strands and an α-helix that adopts a substantially different position compared with closely related Evasin-1. Further investigation into E66S CCL5-Evasin-4 complex formation with NMR spectroscopy showed that residues of the N terminus are involved in binding to CCL5. The peptide derived from the N-terminal region of Evasin-4 possessed nanomolar affinity to CCL5 and inhibited CCL5 activity in monocyte migration assays. This suggests that Evasin-4 derivatives could be used as a starting point for the development of anti-inflammatory drugs.

PubMed: 32817341
DOI: 10.1074/jbc.RA120.013891

実験手法

X-RAY DIFFRACTION (1.69 Å)