Trigramin: primary structure and its inhibition of von Willebrand factor binding to glycoprotein IIb/IIIa complex on human platelets.
Trigramin, a naturally occurring peptide purified from Trimeresurus gramineus (T. stejnegeri formosensis) snake venom, inhibits platelet aggregation and the binding of 125I-fibrinogen to ADP-stimulated platelets (Ki = 2 X 10(-8) M) without affecting the platelet-release reaction. 125I-trigramin binds to ADP-stimulated and to chymotrypsin-treated normal platelets but not to thrombasthenic platelets. 125I-trigramin binding to platelets is blocked by monoclonal antibodies directed against the glycoprotein IIb/IIIa complex and by Arg-Gly-Asp-Ser (RGDS) [Huang et al. (1987) J. Biol. Chem. 262, 161]. We determined the primary structure of trigramin, which is composed of a single polypeptide chain of 72 amino acid residues and six disulfide bridges. The molecular weight of trigramin calculated on the basis of amino acid sequence was 7500, and the average pI was 5.61. An RGD sequence appeared in the carboxy-terminal domain of trigramin. An amino-terminal fragment (7-33) of trigramin showed 39% homology with a region (1555-1581) of von Willebrand factor (vWF). Trigramin also showed 36% identity in a 42 amino acid overlap and 53% identity in a 15 amino acid overlap when compared with two adhesive proteins, collagen alpha 1 (I) and laminin B1, respectively. Trigramin blocked binding of human vWF to the glycoprotein IIb/IIIa complex in thrombin-activated platelets in a dose-dependent manner. Reduction of trigramin resulted in a marked decrease in its ability to block vWF binding to human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
Huang
T F
TF
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Republic of China.
Holt
J C
JC
Kirby
E P
EP
Niewiarowski
S
S
D000595:Amino Acid Sequence; D000818:Animals; D003435:Crotalid Venoms / Q000737:chemistry; D005340:Fibrinogen / Q000037:antagonists & inhibitors*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D012911:Snakes; D014841:von Willebrand Factor / Q000378:metabolism*
D003435:Crotalid Venoms; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; C054194:trigramin; D005340:Fibrinogen; D010447:Peptide Hydrolases