title: Platelet receptor recognition domains on the alpha chain of human fibrinogen: structure-function analysis.
abstract: We have previously shown that the alpha chain of human fibrinogen interacts directly with ADP-activated human platelets [Hawiger, J., Timmons, S., Kloczewiak, M., Strong, D. D., & Doolittle, R. F. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 2068]. Now, we report that platelet receptor recognition domains are localized on two CNBr fragments of the human fibrinogen alpha chain. They encompass residues 92-147 and 518-584, which inhibit 125I-fibrinogen binding to ADP-stimulated platelets. The inhibitory CNBr fragment alpha 92-147 contains the RGD sequence at residues 95-97. Synthetic peptides encompassing this sequence were inhibitory while peptide 99-113 lacking the RGD sequence was inactive. The synthetic peptide RGDF, corresponding to residues alpha 95-98, inhibited the binding of 125I-fibrinogen to ADP-treated platelets (IC50 = 2 microM). However, the peptides containing sequence RGDF, with residues preceding Arg95 or following Phe98, were less inhibitory. It appears that the sequence alpha 95-98 constitutes a platelet receptor recognition domain which is constrained by flanking residues. The second inhibitory CNBr fragment, alpha 518-584, also contains the sequence RGD at positions 572-574. Synthetic peptides overlapping this sequence were inhibitory, while peptides lacking the sequence RGDS were not reactive. Thus, another platelet reactive site on the alpha chain encompasses residues 572-575 containing sequence RGDS. In conclusion, the platelet receptor recognition domains on the human fibrinogen alpha chain in the amino-terminal and in the carboxy-terminal zones contain the ubiquitous cell recognition sequence RGD shared with other known adhesive proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts.
authors.forename: J
authors.initials: J
authors.lastname: Hawiger
authors.forename: M
authors.initials: M
authors.lastname: Kloczewiak
authors.forename: M A
authors.initials: MA
authors.lastname: Bednarek
authors.forename: S
authors.initials: S
authors.lastname: Timmons
mesh_terms: D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification; D010455:Peptides / Q000138:chemical synthesis; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*
chemical_list: D046911:Macromolecular Substances; D010446:Peptide Fragments; D010455:Peptides; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen