A synthetic nonapeptide derived from the sequence of a platelet type I collagen receptor inhibits type I collagen-mediated platelet aggregation.
We have cloned the platelet receptor for type I collagen, but the structure-function of the receptor has not been completely established. The purpose of this investigation was to identify a collagen binding site(s) of the platelet receptor. Three peptides were synthesized chemically. Each peptide serves as an inhibitor of type I collagen-induced platelet aggregation, ATP release, platelet protein phosphorylation, and platelet adhesion to artificial matrices and aortic segments. We show that a nonapeptide specifically inhibits type I collagen-induced platelet aggregation and the release of ATP in a dose-dependent fashion. The peptide also inhibits the binding of radiolabeled alpha (I) chain to washed platelets, the adhesion of radiolabeled platelets to type I collagen-coated petri dishes, rabbit aortic segments, and platelet protein phosphorylation. Deletion of this peptide region of the cloned cDNA abolishes the inhibitory effect of the recombinant protein on type I collagen-induced platelet aggregation. These findings support the likelihood that the nonapeptide forms part of the binding site of the platelet receptor for type I collagen.
Chiang
T M
TM
Veterans Affairs Medical Center and the Department of Medicine, University of Tennessee-Memphis, 38104, USA. chiang@utmem2.utmem.edu
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003094:Collagen / Q000494:pharmacology*; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D016023:Integrins / Q000235:genetics*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011817:Rabbits; D038981:Receptors, Collagen
D017931:DNA Primers; D018076:DNA, Complementary; D016023:Integrins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D038981:Receptors, Collagen; D003094:Collagen