Identification of a novel binding site to the integrin alphaIIbbeta3 located in the C-terminal heparin-binding domain of human plasma fibronectin.
Fibronectin has been shown to bind to integrin alphaIIbbeta3 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 Ala1704 to Glu1718 (designated F1) from this fragment inhibited binding of 125I-labeled 29-kDa fragment of fibronectin to thrombin-stimulated platelets and ADP-induced aggregation. The F1 peptide bound directly to alphaIIbbeta3 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 Ala1704 to Glu1718. Binding of 125I-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 alphaIIbbeta3-binding domain(s) in fibronectin may also play some role for prevention of thrombus formation by direct interaction with alphaIIbbeta3.
Mohri
H
H
First Department of Internal Medicine, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236, Japan.
Tanabe
J
J
Katoh
K
K
Okubo
T
T
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism; D005353:Fibronectins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011485:Protein Binding; D013917:Thrombin / Q000494:pharmacology
D005353:Fibronectins; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000244:Adenosine Diphosphate; D013917:Thrombin