A synthetic nonapeptide derived from the sequence of a platelet type I collagen receptor inhibits type 1 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 th is investigation was to identify a collagen binding site(s) of the pl atelet receptor. Three peptides were synthesized chemically. Each peptide s erves as an inhibitor of type I collagen-induced platelet aggregation, ATP release, platelet protein phosphorylation, and platelet adhesion to artific ial matrices and aortic segments. We show that a nonapeptide specifically i nhibits type I collagen-induced platelet aggregation and the release of ATP in a dose-dependent fashion. The peptide also inhibits the binding of radi olabeled alpha1(I) chain to washed platelets, the adhesion of radiolabeled platelets to type I collagen-coated petri dishes, rabbit aortic segments, a nd 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 li kelihood that the nonapeptide forms part of the binding site of the platele t receptor for type I collagen.