Snake C-type lectin-like proteins and platelet receptors.
Snake venoms are complex mixtures of biologically active proteins and peptides. Many affect haemostasis by activating or inhibiting coagulant factors or platelets, or by disrupting endothelium. 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 GPIb, alpha2beta1 and GPVI. Simple heterodimeric GPIb-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 GPVI while another series affects platelet function via integrin alpha2beta1. Some act by inducing VWF to bind to GPIb. 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.
Clemetson
Kenneth J
KJ
Theodor Kocher Institute, University of Berne, Berne, Switzerland.
Lu
Qiumin
Q
Clemetson
Jeannine M
JM
D000818:Animals; D001792:Blood Platelets / Q000737:chemistry; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D012910:Snake Venoms / Q000737:chemistry*
D037181:Lectins, C-Type; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D012910:Snake Venoms