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Monoclonal antibodies to ligand-occupied conformers of integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) alter receptor affinity, specificity, and function
Occupancy of integrin receptors induces conformational changes in the receptor, resulting in exposure of novel interactive sites termed ligand-induced binding sites (LIBS). We report here that Fab fragments of certain antibodies against LIBS on integrin alpha IIb beta 3 (platelet glycoprotein IIb-II...
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Published in: | The Journal of biological chemistry 1991-09, Vol.266 (26), p.17106-17111 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Occupancy of integrin receptors induces conformational changes in the receptor, resulting in exposure of novel interactive
sites termed ligand-induced binding sites (LIBS). We report here that Fab fragments of certain antibodies against LIBS on
integrin alpha IIb beta 3 (platelet glycoprotein IIb-IIIa) block platelet aggregation. Thus, certain LIBS or the regions surrounding
them may participate in events required for platelet aggregation. In addition, certain anti-alpha IIb beta 3 LIBS Fab fragments
stimulated platelet aggregation. This was due to induction of fg binding to alpha IIb beta 3, apparently by shifting a conformational
equilibrium between a "resting" and an "activated" state of alpha IIb beta 3. Some of the activating anti-LIBS Fab fragments
also induced high affinity fibronectin binding to alpha IIb beta 3, whereas others did not. Thus, changes in the conformation
of this integrin modulate both the specificity and affinity of ligand recognition. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/s0021-9258(19)47346-8 |