Snake venom modulators of platelet adhesion receptors and their ligands

In thrombosis, platelet aggregation is initiated by a specific membrane gly coprotein (GP) Ib-IX-V complex binding to its adhesive ligand, von Willebra nd factor, in the matrix of ruptured atherosclerotic plaques or in plasma e xposed to high hydrodynamic shear stress. This process closely resembles no rmal haemostasis at high shear, where GP Ib-IX-V-dependent platelet adhesio n to von Willebrand factor in the injured blood vessel wall initiates plate let activation and integrin alpha IIb beta 3 (GP IIb-IIIa)-dependent platel et aggregation. At low shear, other receptors such as those that bind colla gen, the integrin alpha 2 beta 1 (GP Ia-IIa) or GP VI, mediate platelet adh esion. Recently, snake venom proteins have been identified that selectively modulate platelet function, either promoting or inhibiting platelet aggreg ation by targeting GP Ib-IX-V, alpha 2 beta 1, GP VI, alpha IIb beta 3, or their respective ligands. Interestingly, these venom proteins typically bel ong to one of two major protein families, the C-type lectin family or the m etalloproteinase-disintegrins. This review focuses on recent insights into structure-activity relationships of snake venom proteins that regulate plat elet function, and the ways in which these novel probes have contributed in unexpected ways to our understanding of the molecular mechanisms underlyin g thrombosis. (C) 2000 Elsevier Science Ltd. All rights reserved.