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5O46

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

Summary for 5O46
Entry DOI10.2210/pdb5o46/pdb
DescriptorIristatin, GLYCEROL (3 entities in total)
Functional Keywordscystatin, protease inhibitor, tick, saliva, hydrolase inhibitor
Biological sourceIxodes ricinus
Total number of polymer chains2
Total formula weight27978.17
Authors
Busa, M.,Rezacova, P.,Kotal, J.,Kotsyfakis, M.,Mares, M. (deposition date: 2017-05-26, release date: 2018-06-13, Last modification date: 2024-11-13)
Primary citationKotal, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.76 Å)
Structure validation

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