|
|
 Previous Article | Table of Contents | Next Article 
Immobilized Arg-Gly-Asp (RGD) peptides of varying lengths as structural
probes of the platelet glycoprotein IIb/IIIa receptor
JH Beer, KT Springer and BS Coller
Division of Hematology, State University of New York, Stony Brook 11794.
The interactions between ligands containing the recognition sequence
arginine-glycine-aspartic acid (RGD) and integrin receptors are important
in many cell-cell and cell-protein interactions. The platelet contains five
integrin receptors and they contribute significantly to platelet adhesion
and aggregation. To investigate the RGD binding domains on platelet
integrins, we immobilized a series of RGD peptides containing variable
numbers of glycine residues [(G)n-RGDF] on polyacrylonitrile beads and
evaluated the ability of the beads to interact with platelets. With native
platelets, virtually no interaction occurred with G1-RGDF beads, but the
interactions increased as the number of glycine residues increased,
plateauing with the G9- RGDF and G11-RGDF beads. ADP pretreatment enhanced
the interactions with all of the beads, whereas prostaglandin E1
pretreatment eliminated the interactions with the shortest peptide beads,
but only partially inhibited interactions with the longer peptide beads.
Monoclonal antibodies to glycoprotein (GP) IIb/IIIa were most effective in
inhibiting the interactions, but antibodies to GPIIb/IIIa with similar
inhibitory effects on fibrinogen binding varied dramatically in their
ability to inhibit the interaction between platelets and immobilized RGD
peptides. Our data indicate that the majority of RGD binding sites on
GPIIb/IIIa can be reached by peptides that extend out approximately 11 to
32 A from the surface of the bead, and these results are in accord with the
dimensions of integrin receptors deduced from electron microscopy.
Activation of GPIIb/IIIa facilitates the interactions, but platelet
inhibition fails to eliminate the interactions with the longer peptide
beads, suggesting that access to the RGD binding site on at least a
fraction of the GPIIb/IIIa receptors is always possible for preferred
ligands. Finally, we found that the G3-RGDF peptide beads were uniquely
sensitive to the activation state of the GPIIb/IIIa receptor.
Volume 79,
Issue 1,
pp. 117-128,
01/01/1992
Copyright © 1992 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Artoni, J. Li, B. Mitchell, J. Ruan, J. Takagi, T. A. Springer, D. L. French, and B. S. Coller
Inaugural Article: Integrin {beta}3 regions controlling binding of murine mAb 7E3: Implications for the mechanism of integrin {alpha}IIb{beta}3 activation
PNAS,
September 7, 2004;
101(36):
13114 - 13120.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R.C. Liddington and M.H. Ginsberg
Integrin activation takes shape
J. Cell Biol.,
September 3, 2002;
158(5):
833 - 839.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Mans, A. I. Louw, and A. W. H. Neitz
Savignygrin, a Platelet Aggregation Inhibitor from the Soft Tick Ornithodoros savignyi, Presents the RGD Integrin Recognition Motif on the Kunitz-BPTI Fold
J. Biol. Chem.,
June 7, 2002;
277(24):
21371 - 21378.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Yan, D. D. Hu, S. K. Knowles, and J. W. Smith
Probing Chemical and Conformational Differences in the Resting and Active Conformers of Platelet Integrin alpha IIbbeta 3
J. Biol. Chem.,
March 15, 2000;
275(10):
7249 - 7260.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. D. Hu, C. A. White, S. Panzer-Knodle, J. D. Page, N. Nicholson, and J. W. Smith
A New Model of Dual Interacting Ligand Binding Sites on Integrin alpha IIbbeta 3
J. Biol. Chem.,
February 19, 1999;
274(8):
4633 - 4639.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Krammer, H. Lu, B. Isralewitz, K. Schulten, and V. Vogel
Forced unfolding of the fibronectin type III module reveals a tensile molecular recognition switch
PNAS,
February 16, 1999;
96(4):
1351 - 1356.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Yuan, P. Primakoff, and D. G. Myles
A Role for the Disintegrin Domain of Cyritestin, a Sperm Surface Protein Belonging to the ADAM Family, in Mouse Sperm-Egg Plasma Membrane Adhesion and Fusion
J. Cell Biol.,
April 7, 1997;
137(1):
105 - 112.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. S. Coller, D. Lang, and L. E. Scudder
Rapid and Simple Platelet Function Assay to Assess Glycoprotein IIb/IIIa Receptor Blockade
Circulation,
February 18, 1997;
95(4):
860 - 867.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
T. J. Kunicki, D. S. Annis, Y.-J. Deng, J. C. Loftus, and S. J. Shattil
A Molecular Basis for Affinity Modulation of Fab Ligand Binding to Integrin alpha IIbbeta 3
J. Biol. Chem.,
August 23, 1996;
271(34):
20315 - 20321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Yan and J. W. Smith
A Redox Site Involved in Integrin Activation
J. Biol. Chem.,
December 15, 2000;
275(51):
39964 - 39972.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
