Structure Comparison of Salivary Serpins from Ixodes ricinus

B. Kaščáková¹, J. Chmelař¹, T. Prudnikova^1,2, M. Kutý^1,2, I. Kutá Smatanová^1,2

¹University of South Bohemia, Faculty of Science, Branisovska 31, CZ-37005 Ceske Budejovice, Czech Republic

²Institute of Microbiology, Center for Nanobiology and Structural Biology, ASCR, Zámek 136, Nové Hrady, Czech Republic

chmelar@prf.jcu.cz

The serpins are a large superfamily of structurally conserved proteins that are widely distributed [1]. Our structural study is focused on serpins, serine protease inhibitors, found in tick saliva. This group of proteins has primarily immunological and haemostatic functions, but their functions can vary. The tick serpins act as modulators of immune responses by using their anti-coagulation, anti-complementary functions and play role in immunosuppression [2].

The serpins rearrange their structural conformation required for inhibitory activity. The secondary structure typically consists of 3 β-barrels, 9 α-helices and exposed, flexible reactive center loop (RCL) that contains proteinase recognition site. There are different types of conformation and each of these structural rearrangements is important in the inhibitory pathway. The process of serine proteinase inhibition required irreversible suicide substrate mechanism [3].

Structural and functional studies of inhibitory serpins help understand the serpinopathies, diseases such as cirrhosis, hypertension or familial dementia. Here, we present the crystal structures of two serpins found in tick saliva of Ixodes ricinus (iripin3 and IRS-4) compared to the structure of Ixodes ricinus serpin 2 (IRS-2) describe previously [4].

1. J. Potempa, E. Korzus & J. Travis (1994) J. Biol. Chem. 269, 15957-15960.

2. Ooi, C. P., Haines, L. R., Southern, D. M., Lehane, M. J., & Acosta-Serrano, A. (2015). PLoS Negl. Trop. Dis. 9:e3448. doi: 10.1371/journal.pntd.0003448

3. P. G. W. Gettins, P. A. Patston & S. T. Olson(eds) (1996) Serpins: Structure, Function and Biology, Molecular  biology Intelligence Unit, R. G. Landes Co., and Chapman & Hall, Austin, TX

4. J. Chmelar, C. J. Oliveira, P. Rezacova, I. M. B. Francischetti, Z. Kovarova, G. Pejler, P. Kopacek, J.M. C. Ribeiro, M. Mares, J. Kopecky & M. Kotsyfakis; Blood 2011; 117 (2): 736–744. doi: https://doi.org/10.1182/blood-2010-06-293241

This research is supported by GACR 19-14704Y, ERDF No. CZ.02.1.01/0.0/0.0/15_003/000041 and GAJU 04-017/2019/P.