5O46

Crystal structure of Iristatin, a secreted salivary cystatin from the hard tick Ixodes ricinus

5O46 の概要

• エントリーDOI: 10.2210/pdb5o46/pdb
• 分子名称: Iristatin, GLYCEROL (3 entities in total)
• 機能のキーワード: cystatin, protease inhibitor, tick, saliva, hydrolase inhibitor
• 由来する生物種: Ixodes ricinus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27978.17

構造登録者

Busa, M.,Rezacova, P.,Kotal, J.,Kotsyfakis, M.,Mares, M. (登録日: 2017-05-26, 公開日: 2018-06-13, 最終更新日: 2024-11-13)

主引用文献

Kotal, J.,Stergiou, N.,Busa, M.,Chlastakova, A.,Berankova, Z.,Rezacova, P.,Langhansova, H.,Schwarz, A.,Calvo, E.,Kopecky, J.,Mares, M.,Schmitt, E.,Chmelar, J.,Kotsyfakis, M.
The structure and function of Iristatin, a novel immunosuppressive tick salivary cystatin.
Cell.Mol.Life Sci., 76:2003-2013, 2019

PubMed Abstract: To successfully feed, ticks inject pharmacoactive molecules into the vertebrate host including cystatin cysteine protease inhibitors. However, the molecular and cellular events modulated by tick saliva remain largely unknown. Here, we describe and characterize a novel immunomodulatory cystatin, Iristatin, which is upregulated in the salivary glands of feeding Ixodes ricinus ticks. We present the crystal structure of Iristatin at 1.76 Å resolution. Purified recombinant Iristatin inhibited the proteolytic activity of cathepsins L and C and diminished IL-2, IL-4, IL-9, and IFN-γ production by different T-cell populations, IL-6 and IL-9 production by mast cells, and nitric oxide production by macrophages. Furthermore, Iristatin inhibited OVA antigen-induced CD4 T-cell proliferation and leukocyte recruitment in vivo and in vitro. Our results indicate that Iristatin affects wide range of anti-tick immune responses in the vertebrate host and may be exploitable as an immunotherapeutic.

PubMed: 30747251
DOI: 10.1007/s00018-019-03034-3

実験手法

X-RAY DIFFRACTION (1.76 Å)