THE HEMORRHAGIN CATROCOLLASTATIN INHIBITS COLLAGEN-INDUCED PLATELET-AGGREGATION BY BINDING TO COLLAGEN VIA ITS DISINTEGRIN-LIKE DOMAIN

Catrocollastatin, a 50 kDa snake venom protein purified from Crotalus atrox, specifically inhibits platelet-collagen adhesion and collagen-i nduced aggregation. Catrocollastatin is composed of an N-terminal doma in, a metalloproteinase domain. a disintegrin-like domain and a cystei ne-rich C-terminal domain, The present studies show that catrocollasta tin exerts its effect by binding to collagen. Based on the amino acid sequence and homology analysis, a cyclic oligopeptide corresponding to a conservative fragment containing the sequence SECD in the disintegr in-like domain has been synthesized. Like its protein parent, the synt hetic peptide inhibits collagen-induced aggregation and possesses the ability to bind to collagen. This is the first snake venom protein wit h a disintegrin-like structure shown to bind to an integrin ligand mat rix molecule instead of an integrin. (C) 1996 Academic Press, Inc.