Snake C-type lectin-like proteins and platelet receptors

Snake venoms are complex mixtures of biologically active proteins and pepticles. Many affect haemostasis by activating or inhibiting coagulant factors or platelets, or by disrupting enclothelium. Snake venom components are classified into various families, such as serine proteases, metalloproteinases, C-type lectin-like proteins, disintegrins and phospholipases. Snake venom C-type lectin-like proteins have a typical fold resembling that in classic C-type lectins such as the selectins and mannose-binding proteins. Many snake venom C-type lectin-like proteins have now been characterized, as heterodimeric structures with alpha and beta subunits that often form large molecules by multimerization. They activate platelets by binding to VWF or specific receptors such as GPlb, alpha(2)beta(1) and GPVl. Simple heterodimeric GPlb-binding molecules mainly inhibit platelet functions, whereas multimeric ones activate platelets. A series of tetrameric snake venom C-type lectin-like proteins activates platelets by binding to GPVl while another series affects platelet function via integrin alpha(2)beta(1)- Some act by inducing VWF to bind to GPlb. Many structures of these proteins, often complexed with their ligands, have been determined. Structure-activity studies show that these proteins are quite complex despite similar backbone folding. Snake C-type lectin-like proteins often interact with more than one platelet receptor and have complex mechanisms of action. Copyright (c) 2005 S. Karger AG, Basel.