Snake venom probes of platelet adhesion receptors and their ligands

摘要

Snake venom proteins that modulate platelet adhesive interactions are chiefly from either of two main structural families: the C-type lectin-like family, or the metalloproteinase-disintegrins. Snake venom probes from both families selectively target platelet adhesion receptors, including glycoprotein (GP) Ib-IX-V, GP VI, alpha(2)beta(1) and alpha IIb beta(3) (GP IIb-IIIa). These receptors act together to mediate platelet adhesion, activation and aggregation (thrombus formation) under hydrodynamic shear stress in flowing blood. The receptors are members of the leucine-rich repeat family (GP Ib-IX-V), the immunoglobulin superfamily (GP VI), or integrins (alpha(2)beta(1), alpha IIb beta(3)). In addition, adhesive glycoproteins in matrix and/or plasma such as von Willebrand factor (that binds GP Ib alpha and alpha IIb beta 3), collagen (that binds GP V, GP VI and alpha(2)beta(1)), or fibrinogen (that binds alpha IIb beta(3)), are also targeted by C-type lectin family or metalloproteinase-disintegrin snake venom proteins. Emerging structural and functional evidence is beginning to explain how interactions between the conserved structural module-domains that make up these mammalian and snake proteins are regulated. Whether homologous adhesion/counter-receptors on platelets and other vascular cells are also potential snake venom targets is as yet largely unexplored. (c) 2005 Elsevier Ltd. All rights reserved.