[HTML][HTML] Monoclonal antibodies to ligand-occupied conformers of integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) alter receptor affinity, specificity, and function.

AL Frelinger 3rd, XP Du, EF Plow… - Journal of Biological …, 1991 - Elsevier
Journal of Biological Chemistry, 1991Elsevier
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 …
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.
Elsevier