Institute of Parasitology, Biology Centre, Academy of Sciences of the Czech Republic, Branišovská 1160/31, 37005 České Budějovice, Czech Republic.
Department of Medical Biology, Faculty of Science, University of South Bohemia in České Budějovice, Branišovská 1760c, 37005 České Budějovice, Czech Republic.
Int J Mol Sci. 2021 May 20;22(10):5371. doi: 10.3390/ijms22105371.
The hard tick is a vector of Lyme disease and tick-borne encephalitis. Host blood protein digestion, essential for tick development and reproduction, occurs in tick midgut digestive cells driven by cathepsin proteases. Little is known about the regulation of the digestive proteolytic machinery of . Here we characterize a novel cystatin-type protease inhibitor, mialostatin, from the midgut. Blood feeding rapidly induced mialostatin expression in the gut, which continued after tick detachment. Recombinant mialostatin inhibited a number of digestive cysteine cathepsins, with the greatest potency observed against cathepsin L isoforms, with which it co-localized in midgut digestive cells. The crystal structure of mialostatin was determined at 1.55 Å to explain its unique inhibitory specificity. Finally, mialostatin effectively blocked in vitro proteolysis of blood proteins by midgut cysteine cathepsins. Mialostatin is likely to be involved in the regulation of gut-associated proteolytic pathways, making midgut cystatins promising targets for tick control strategies.
硬蜱是莱姆病和蜱传脑炎的传播媒介。宿主血液蛋白的消化对于蜱的发育和繁殖至关重要，它发生在蜱的中肠消化细胞中，由组织蛋白酶蛋白酶驱动。关于硬蜱的消化蛋白水解机制的调控知之甚少。在这里，我们从硬蜱的中肠中鉴定了一种新型的半胱氨酸蛋白酶抑制剂，miallostatin。吸血会迅速诱导肠道中miallostatin 的表达，并且在蜱脱离后仍会继续。重组的 miallostatin 抑制了许多硬蜱的消化半胱氨酸组织蛋白酶，对组织蛋白酶 L 同工酶的抑制作用最大，与组织蛋白酶 L 同工酶在中肠消化细胞中共定位。miallostatin 的晶体结构在 1.55 Å 下被确定，以解释其独特的抑制特异性。最后，miallostatin 有效地阻止了中肠半胱氨酸组织蛋白酶对血液蛋白的体外蛋白水解。miallostatin 可能参与了肠道相关蛋白水解途径的调控，使中肠半胱氨酸蛋白酶抑制剂成为控制蜱的有前途的靶点。
