Structural dynamics of Rhipicephalus microplus serpin-3

Cattle ticks, Rhipicephalus (Boophilus) microplus, have a serious impact on livestock worldwide. For tick control, host vaccination is more sustainable than chemical. Salivary serpin (serine protease inhibitor) from R. microplus (RmS-3) is a potential anti-tick vaccine candidate antigen. Like other serpins, RmS-3 has a suicide inhibition mechanism, where the reactive centre loop (RCL) is cleaved and then inserted into the main beta-pleated sheet. This causes the breakdown of serpin into two regions (core domain and cleaved polypeptide). A small sequence variation of RmS-3 was observed among specimens in Thailand included three extra amino acids (T147, K180, N193). Molecular Dynamics simulations of the previously reported (Micro) and the novel Thai RmS-3 (Thai) were conducted in comparison. Overall, Micro is more rigid than Thai. Having additional T147 and K180 enhance the structural flexibility in Thai. Both residues are located close to areas that perform a distinct conformational change, so T147 and K180 may impact inhibitory activity of Thai RmS-3. In contrast, N193 seems to have a minor effect. A presence of T147 and K180 in Thai seems to cause significant differences in structural dynamics which may lead to different degrees of inhibition activity. Further experimental studies are required.

Automated summary

The study revealed a small sequence variation of RmS-3 among specimens in Thailand, potentially impacting the inhibitory activity of the anti-tick vaccine candidate. Further experimental studies are required to investigate the structural dynamics and inhibitory activity.