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-induced aggregation. Catrocollastatin is composed of an N-terminal domain, a metalloproteinase domain, a disintegrin-like domain and a cysteine-rich C-terminal domain. The present studies show that catrocollastatin 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 disintegrin-like domain has been synthesized. Like its protein parent, the synthetic peptide inhibits collagen-induced aggregation and possesses the ability to bind to collagen. This is the first snake venom protein with a disintegrin-like structure shown to bind to an integrin ligand matrix molecule instead of an integrin.
Zhou
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Q
Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Dangelmaier
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C
Smith
J B
JB
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D003094:Collagen / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D003435:Crotalid Venoms / Q000494:pharmacology; D019483:Disintegrins; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014316:Tritium
D003435:Crotalid Venoms; D019483:Disintegrins; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D014316:Tritium; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D008666:Metalloendopeptidases; C093237:catrocollastatin