Laboratory of Genomics and Proteomics of Disease Vectors, Institute of Parasitology, Biology Centre, Czech Academy of Sciences, 37005 Ceske Budejovice, Czech Republic.
Laboratory of Hematophagous Arthropods, Department of Parasitology, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.
Int J Mol Sci. 2023 Jan 13;24(2):1556. doi: 10.3390/ijms24021556.
Kunitz domain-containing proteins are ubiquitous serine protease inhibitors with promising therapeutic potential. They target key proteases involved in major cellular processes such as inflammation or hemostasis through competitive inhibition in a substrate-like manner. Protease inhibitors from the Kunitz superfamily have a low molecular weight (18-24 kDa) and are characterized by the presence of one or more Kunitz motifs consisting of α-helices and antiparallel β-sheets stabilized by three disulfide bonds. Kunitz-type inhibitors are an important fraction of the protease inhibitors found in tick saliva. Their roles in inhibiting and/or suppressing host homeostatic responses continue to be shown to be additive or synergistic with other protease inhibitors such as cystatins or serpins, ultimately mediating successful blood feeding for the tick. In this review, we discuss the biochemical features of tick salivary Kunitz-type protease inhibitors. We focus on their various effects on host hemostasis and immunity at the molecular and cellular level and their potential therapeutic applications. In doing so, we highlight that their pharmacological properties can be exploited for the development of novel therapies and vaccines.
Kunitz 结构域蛋白是广泛存在的丝氨酸蛋白酶抑制剂，具有有前途的治疗潜力。它们通过竞争性抑制底物样方式靶向参与炎症或止血等主要细胞过程的关键蛋白酶。Kunitz 超家族的蛋白酶抑制剂分子量低（18-24 kDa），其特征是存在一个或多个 Kunitz 基序，由α-螺旋和反平行β-片层组成，并由三个二硫键稳定。Kunitz 型抑制剂是在蜱唾液中发现的蛋白酶抑制剂的重要组成部分。它们在抑制和/或抑制宿主动态平衡反应方面的作用与其他蛋白酶抑制剂（如半胱氨酸蛋白酶抑制剂或丝氨酸蛋白酶抑制剂）继续表现出相加或协同作用，最终介导蜱的成功吸血。在这篇综述中，我们讨论了蜱唾液中的 Kunitz 型蛋白酶抑制剂的生化特征。我们重点讨论了它们在分子和细胞水平上对宿主止血和免疫的各种影响及其潜在的治疗应用。这样做时，我们强调可以利用它们的药理学特性来开发新的治疗方法和疫苗。
