Snake venom probes of platelet adhesion receptors and their ligands.
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, alpha2beta1 and alphaIIbbeta3 (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 (alpha2beta1, alphaIIbbeta3). In addition, adhesive glycoproteins in matrix and/or plasma such as von Willebrand factor (that binds GP Ibalpha and alphaIIbbeta3), collagen (that binds GP V, GP VI and alpha2beta1), or fibrinogen (that binds alphaIIbbeta3), 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.
Wijeyewickrema
Lakshmi C
LC
Department of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, Vic. 3168, Australia.
Berndt
Michael C
MC
Andrews
Robert K
RK
D000818:Animals; D019483:Disintegrins / Q000378:metabolism*; D007136:Immunoglobulins / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D045726:Metalloproteases / Q000378:metabolism*; D010973:Platelet Adhesiveness / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D012910:Snake Venoms / Q000201:enzymology / Q000378:metabolism*; D012911:Snakes; D013329:Structure-Activity Relationship
D019483:Disintegrins; D007136:Immunoglobulins; D016023:Integrins; D037181:Lectins, C-Type; D010980:Platelet Membrane Glycoproteins; D012910:Snake Venoms; D045726:Metalloproteases