The precise localization of the epitopes for six monoclonal antibodies specific for the N-terminal region of human platelet glycoprotein IIIa (GPIIIa) was determined. The epitope for P37, a monoclonal antibody that inhibits platelet aggregation, was found at GPIIIa 101-109, flanked by the epitopes for P23-3 (GPIIIa 16-28), P23-4 (GPIIIa 83-91), P23-5 (GPIIIa 67-73), P23-7 (GPIIIa 114-122) and P40 (GPIIIa 262-302), and very close to the early chymotryptic cleavage site of GPIIIa in whole platelets (Phe-100). When the amino acid sequence of GPIIIa was searched for peptide sequences hydropathically complementary to the fibrinogen gamma-chain C-terminal (gamma 400-411) and A alpha-chain RGD-containing peptides, none was found for the gamma 400-411, two (GPIIIa 128-132 and 380-384) were found complementary to fibrinogen A alpha 571-575 and two (GPIIIa 109-113 and 129-133) were found for A alpha 94-99. Two of these putative fibrinogen-binding sites overlap with each other, and a third one overlaps with the epitope for P37. These findings reinforce the earlier suggestion that the N-terminal region of GPIIIa is involved in fibrinogen binding, and suggest the existence in GPIIIa of either multiple or alternative RGD-binding sites or one RGD-binding domain with several moieties. Finally, early chymotryptic cleavage of GPIIIa in whole platelets liberates to the soluble fraction the peptide stretch Ser-101-Tyr-348, which carries the epitope for P37 and the putative binding sites for fibrinogen. The rest of the molecule, together with the GPIIb-resistant moiety, remains membrane-bound. This leads us to propose that the fibrinogen-binding domain of GPIIIa is not involved in the binding to GPIIb to form the Ca2(+)-dependent GPIIb-GPIIIa complex.
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March 1991
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Research Article|
March 01 1991
Further studies on the topography of the N-terminal region of human platelet glycoprotein IIIa. Localization of monoclonal antibody epitopes and the putative fibrinogen-binding sites
J J Calvete;
J J Calvete
*Instituto de Química Física, C.S.I.C., Calle Serrano 119, 2800 Madrid, Spain.
†Max-Planck Institut für Biochemie, D-8033 Martinsried/Miinchen, Federal Republic of German
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J Arias;
J Arias
*Instituto de Química Física, C.S.I.C., Calle Serrano 119, 2800 Madrid, Spain.
†Max-Planck Institut für Biochemie, D-8033 Martinsried/Miinchen, Federal Republic of German
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M V Alvarez;
M V Alvarez
*Instituto de Química Física, C.S.I.C., Calle Serrano 119, 2800 Madrid, Spain.
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M M Lopez;
M M Lopez
*Instituto de Química Física, C.S.I.C., Calle Serrano 119, 2800 Madrid, Spain.
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A Henschen;
A Henschen
†Max-Planck Institut für Biochemie, D-8033 Martinsried/Miinchen, Federal Republic of German
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J González-Rodríguez
J González-Rodríguez
*Instituto de Química Física, C.S.I.C., Calle Serrano 119, 2800 Madrid, Spain.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1991 The Biochemical Society, London
1991
Biochem J (1991) 274 (2): 457–463.
Citation
J J Calvete, J Arias, M V Alvarez, M M Lopez, A Henschen, J González-Rodríguez; Further studies on the topography of the N-terminal region of human platelet glycoprotein IIIa. Localization of monoclonal antibody epitopes and the putative fibrinogen-binding sites. Biochem J 1 March 1991; 274 (2): 457–463. doi: https://doi.org/10.1042/bj2740457
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