Serpins are a large superfamily of structurally conserved protease inhibitors that are widely distributed in nature [1]. A structural study of serpins found in tick saliva revealed members' uniformity of structure but not their functions. This group of proteins has primarily immunological and haemostatic functions, but their functions can vary according to their specificity. The tick serpins act as modulators of immune responses by using their anti-coagulation, and anti-complementary functions and play role in immunosuppression [2].
The structural transition to the different conformation is required for inhibitory activity. The secondary structure typically consists of 3 β-barrels, 7-9 α-helices and an exposed, flexible reactive center loop that acts as proteinase “bait”. There are different types of conformation and each of these structural rearrangements is important in the inhibitory pathway. The serpins are irreversible inhibitors that adapt the suicide substrate mechanism [3].
Iripin-4 with hitherto unexplained function, crystallized in two different structural conformations. The native structure was solved at 2.3 Å resolution and the structure of cleaved conformation at 2.0 Å resolution. Furthermore, structural changes during the reactive-centre loop transition from native to cleaved conformation were observed. In addition to this finding, we confirm that the main substrate-recognition site for the inhibitory mechanism is represented by Glu341. Further research on Iripin-4 should focus on the functional analysis of this interesting serpin.
This research was supported by European Regional Development Fund-Project, MEYS (No. CZ.02.1.01/0.0/0.0/15_003/0000441); by the Grant Agency of the Czech Republic (Grant No. 19-14704Y) and by the Grant Agency of the University of South Bohemia (grant No. 105/2019/P and 04-039/2019/P).