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Further characterization of the loop structure of platelet glycoprotein
IIIa: partial mapping of functionally significant glycoprotein IIIa
epitopes
WC Kouns, PJ Newman, KJ Puckett, AA Miller, CD Wall, CF Fox, JM Seyer and LK Jennings
Department of Medicine, University of Tennessee, Memphis 38163.
Glycoprotein (GP) IIb-IIIa serves as the platelet fibrinogen receptor.
Studies of the tertiary structure of GPIIIa have shown that the protein has
a large loop structure of at least 325 amino acids in length. To further
characterize this loop structure, intact platelets were digested with
alpha-chymotrypsin. Digestion products were examined using the anti-GPIIIa
monoclonal antibodies (MoAbs) AP3, D3GP3, and C5GP3, as well as the human
alloantibody, anti-PLA1. AP3 recognized GPIIIa digestion products of 109,
95, and 68 Kd. D3GP3 and C5GP3 recognized an additional band of 51 Kd. Time
course digestions demonstrated that the 51-Kd fragment was generated by
proteolysis of the 68-Kd peptide. Sequence analysis of the reduced 51-Kd
peptide showed that this fragment began at amino acid 422. The nonreduced
51-Kd peptide was reactive with antibodies directed against the first 13
amino acids of GPIIIa, demonstrating the presence of a covalently attached
N-terminal peptide. These data suggest that: (1) the minimum length of the
loop structure is at least 384 amino acids; (2) the AP3 epitope is formed
at least in part by a determinant contained within residues 348 to 421; and
(3) the D3GP3 and C5GP3 epitopes are contained within amino acids 422 to
692 of GPIIIa, a region that may be flexible and involved in conformational
changes that occur after ligand binding.
Volume 78,
Issue 12,
pp. 3215-3223,
12/15/1991
Copyright © 1991 by The American Society of Hematology
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