1. An echistatin C-terminal peptide activates GPIIbIIIa binding to fibrinogen, fibronectin, vitronectin and collagen type I and type IV
- Author
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Alan J. Bitonti, P.S. Wright, S.L. Harbeson, V Saudek, and T.J. Owen
- Subjects
Blood Platelets ,Protein domain ,Integrin ,Molecular Sequence Data ,Peptide ,Enzyme-Linked Immunosorbent Assay ,Platelet Membrane Glycoproteins ,Viper Venoms ,Biochemistry ,Humans ,Amino Acid Sequence ,Vitronectin ,Molecular Biology ,Integrin binding ,Glycoproteins ,chemistry.chemical_classification ,Binding Sites ,biology ,Binding protein ,Fibrinogen ,Cell Biology ,Fibronectins ,Fibronectin ,chemistry ,Biophysics ,biology.protein ,Intercellular Signaling Peptides and Proteins ,Collagen ,Glycoprotein ,Peptides ,Platelet Aggregation Inhibitors ,Research Article - Abstract
Integrin binding to proteins often involves recognition of domains containing the arginine-glycine-aspartate (RGD) motif. Different binding affinities and specificities of the integrin-ligand protein interactions involve additional protein domains. The n.m.r. structure of the snake-venom protein echistatin suggested that the C-terminal portion of the molecule might be important, in addition to the RGD domain, in binding to the integrin glycoprotein IIbIIIa (GPIIbIIIa) [Saudek, Atkinson and Pelton (1991) Biochem. 30, 7369-7372]. The synthetic C-terminal peptide, echistatin-(40-49), PRNPHKGPAT, (1) inhibited binding of GPIIbIIIa to immobilized echistatin (IC50 3-6 mM), but did not inhibit binding of GPIIbIIIa to immobilized fibrinogen (up to 5 mM peptide), (2) activated GPIIbIIIa binding to fibronectin and vitronectin, usual ligands for the activated integrin, (3) activated binding of GPIIbIIIa to collagen type I and type IV, proteins not usually regarded as ligands for the integrin, and (4) stimulated 125I-fibrinogen binding by human platelets. These findings argue for an interaction of this non-RGD domain in echistatin with GPIIbIIIa, leading to activation of the integrin and extension of the ligand specificity to include immobilized collagen.
- Published
- 1993