J. Biol. Chem., Vol. 262, Issue 26, 12597-12602, Sep, 1987

Synthetic peptides derived from fibrinogen and fibronectin change the conformation of purified platelet glycoprotein IIb-IIIa

LV Parise, SL Helgerson, B Steiner, L Nannizzi and DR Phillips

The glycoprotein IIb-IIIa complex (GP IIb-IIIa) is a platelet cell- surface receptor for fibrinogen and fibronectin. A carboxyl-terminal decapeptide of the fibrinogen gamma-chain (Leu-Gly-Gly-Ala-Lys-Gln-Ala- Gly-Asp-Val LGGAKQAGDV] and a tetrapeptide (Arg-Gly-Asp-Ser (RGDS] from the fibrinogen alpha-chain and the fibronectin cell-binding domain appear to mediate the binding of these ligands to GP IIb-IIIa. The present study was designed to examine the effects of these and related peptides on the structure of purified platelet GP IIb-IIIa. Treatment of GP IIb-IIIa with various synthetic peptides affected the glycoprotein so that GP IIb alpha became a substrate for hydrolysis by thrombin. The order of potency of these peptides was as follows: RGDS greater than LGGAKQAGDV greater than KGDS greater than RGES. This is the same order of potency in which these peptides inhibit fibrinogen binding to platelets. This effect was time-, temperature-, and concentration-dependent; RGDS induced a half-maximal effect at approximately 60 microM. In addition, RGDS, but not RGES, decreased the intensity of the intrinsic protein fluorescence of GP IIb-IIIa. Finally, the decapeptide or RGDS decreased the sedimentation coefficient of GP IIb-IIIa from 8.5 to 7.7 or 7.4 S, respectively, whereas RGES had a minimal effect. This decrease was accompanied by an increase in the Stoke's radius from 74 to 82 A with RGDS or 85 A with the decapeptide, indicating a peptide-induced unfolding of the GP IIb- IIIa complex. This change in conformation may be related to changes in the distribution and function of GP IIb-IIIa on the platelet surface that occur when adhesive proteins or peptides from the GP IIb-IIIa binding domains of these proteins bind to GP IIb-IIIa.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. L. Frelinger III, M. I. Furman, L. A. Krueger, M. R. Barnard, and A. D. Michelson Dissociation of Glycoprotein IIb/IIIa Antagonists From Platelets Does Not Result in Fibrinogen Binding or Platelet Aggregation Circulation, September 18, 2001; 104(12): 1374 - 1379. [Abstract] [Full Text] [PDF]

				R. R. Hantgan, M. Rocco, C. Nagaswami, and J. W. Weisel Binding of a fibrinogen mimetic stabilizes integrin {alpha}IIb{beta}3's open conformation Protein Sci., August 1, 2001; 10(8): 1614 - 1626. [Abstract] [Full Text] [PDF]

				A. Jedsadayanmata, C.-C. Chen, M. L. Kireeva, L. F. Lau, and S. C.-T. Lam Activation-dependent Adhesion of Human Platelets to Cyr61 and Fisp12/Mouse Connective Tissue Growth Factor Is Mediated through Integrin alpha IIbbeta 3 J. Biol. Chem., August 20, 1999; 274(34): 24321 - 24327. [Abstract] [Full Text] [PDF]

				T. M. Leisner, J. D. Wencel-Drake, W. Wang, and S. C.-T. Lam Bidirectional Transmembrane Modulation of Integrin alpha IIbbeta 3 Conformations J. Biol. Chem., April 30, 1999; 274(18): 12945 - 12949. [Abstract] [Full Text] [PDF]

				K. Peter, M. Schwarz, J. Ylanne, B. Kohler, M. Moser, T. Nordt, P. Salbach, W. Kubler, and C. Bode Induction of Fibrinogen Binding and Platelet Aggregation as a Potential Intrinsic Property of Various Glycoprotein IIb/IIIa (alpha IIbbeta 3) Inhibitors Blood, November 1, 1998; 92(9): 3240 - 3249. [Abstract] [Full Text] [PDF]

				A. Wong, S. M. Hwang, K. Johanson, J. Samanen, D. Bennett, S. W. Landvatter, W. Chen, J. R. Heys, F. E. Ali, T. W. Ku, et al. Binding of [3H]-SK&F 107260 and [3H]-SB 214857 to Purified Integrin alpha IIbbeta 3: Evidence for a Common Binding Site for Cyclic Arginyl-Glycinyl-Aspartic Acid Peptides and Nonpeptides J. Pharmacol. Exp. Ther., April 1, 1998; 285(1): 228 - 235. [Abstract] [Full Text]

				S. R. Simmons, P. A. Sims, and R. M. Albrecht {alpha}IIbß3 Redistribution Triggered by Receptor Cross-Linking Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 3311 - 3320. [Abstract] [Full Text]

				A. J. Pelletier, T. Kunicki, and V. Quaranta Activation of the Integrin alpha(v)beta(3) Involves a Discrete Cation-binding Site That Regulates Conformation J. Biol. Chem., January 19, 1996; 271(3): 1364 - 1370. [Abstract] [Full Text] [PDF]

				N. I. Zolotarjova, G. F. Hollis, and R. Wynn Unusually Stable and Long-lived Ligand-induced Conformations of Integrins J. Biol. Chem., May 11, 2001; 276(20): 17063 - 17068. [Abstract] [Full Text] [PDF]