SNAKE VENOM C-TYPE LECTINS INTERACTING WITH PLATELET RECEPTORS

Abstract

Based on sequence comparison, snake venom components affecting hemostasis have been classified into various families, including serine proteases, metalloproteinases, C-type lectins, disintegrins, and phospholipases. These proteins affect platelet function by binding or degrading von Willebrand factor (VWF) or platelet membrane glycoproteins, activating protease-activated receptors, or modulating ADP release and thromboxane A2 formation. Many snake venom C-type lectins have now been characterized, mostly heterodime ric structures with α and β subunits that are often multimerized to form large molecules. They affect platelet activation by binding to VWF or to specific collagen receptors such as GPIb, α2β1, and GPVI. While simple heterodimeric GPIb-binding molecules mostly inhibit platelet functions, multimeric ones often activate platelets. Some act by inducing VWF to bind to GPIb. Another series of snake venom C-type lectins activates platelets by binding to GPVI, while yet another series affects, platelet function via integrin α2β 1. Snake venom C-type lectins, have a typical fold structure like that in classic C-type lectins, such as the selectins and mannose-binding proteins. More and more structures of these proteins, often complexed with their ligands, have been determined, and structure–activity studies have shown that these proteins are quite a complex group, though with similar backbone folding. Recent studies have shown that snake C-type lectins often interact with more than one platelet receptor and have complex mechanisms of action. It is also noteworthy that snake C-type lectins may act differently in vivo and in vitro.