Structure and function of invertebrate Kunitz serine protease inhibitors

Kunitz type proteins are an important group of ubiquitous protease inhibitors found spanning the evolutionary tree from microbes to mammals. These proteins can have single or multiple Kunitz inhibitory domains linked together, or associated with other domain types. The Kunitz motif comprises a chain of around 60 amino acid residues stabilized by three disulphide bonds. The inhibitory specificity of the Kunitz domain varies with the particular amino acids at the reactive sites and exhibit canonical inhibition. In vertebrates, Kunitz inhibitors play a major role in inflammatory processes while in invertebrates involve in a range of diverse functional roles. This review discusses the structure, mechanism of action and functions of invertebrate Kunitz inhibitors. Venomous invertebrates such as scorpions, cone snails have either Kunitz inhibitors with both neurotoxic and protease inhibitory activity or typical Kunitz type toxins. In parasitic helminths these inhibitors play a major role in providing protection from host digestive protease enzymes. Several proteins having Kunitz domains in nematodes are involved in collagen biosynthesis while some induce IgE-mediated allergic reactions. Most Kunitz inhibitors in blood sucking arthropods function as anti-coagulant factors and several act as a defense against microbial pathogen invaders.

► Kunitz type proteins are a family of serine protease inhibitors.
► They exhibit canonical inhibitory mechanism.
► Kunitz motif consists of six conserved cysteine residues forming three disulphide bonds.
► Kunitz proteins play a crucial role in inflammatory processes in vertebrates.
► Invertebrate Kunitz proteins involve in diverse physiological functions.