Identification of a Novel Binding Site to the Integrin αIIbβ3 Located in the C-terminal Heparin-binding Domain of Human Plasma Fibronectin

Fibronectin has been shown to bind to integrin α IIb β 3 in Arg-Gly-Asp (RGD)-dependent and -independent manners. A recent study has indicated that a 29-kDa dispase-digestive fragment from the C-terminal heparin-binding domain of human plasma fibronectin (lacking RGD sequence) inhibits binding of fibronectin to thrombin-stimulated platelets and ADP-induced aggregation (Tanabe, J., Fujita, H., Iwamatsu, A., Mohri, H., and Ohkubo, T. (1993) J. Biol. Chem. 268, 27143-27147). We provide here the evidence that a peptide corresponding to residues from Ala 1704 to Glu 1718 (designated F1) from this fragment inhibited binding of 125 I-labeled 29-kDa fragment of fibronectin to thrombin-stimulated platelets and ADP-induced aggregation. The F1 peptide bound directly to α IIb β 3 integrin receptor. These results indicate that a novel binding site in the C-terminal heparin-binding region of fibronectin is localized within the residues from Ala 1704 to Glu 1718 . Binding of 125 I-labeled 29-kDa fragment of fibronectin to thrombin-stimulated platelets was not inhibited by RGDS peptide and the 12-residue peptide from the cell-binding domain of fibronectin, suggesting that binding site in the C-terminal heparin-binding domain may be different from those of RGDS and the 12-residue peptide. This additional α IIb β 3 -binding domain(s) in fibronectin may also play some role for prevention of thrombus formation by direct interaction with α IIb β 3 .