Sequence 274-368 in the β3-subunit of the integrin αIIbβ3 provides a ligand recognition and binding domain for the γ-chain of fibrinogen that is independent of platelet activation

Abstract

Several bacterial-expressed recombinant fragments encompassing the extracellular part of the β3 subunit of the integrin αIIbβ3 were shown to recognize and bind soluble and immobilized forms of fibrinogen. Two of them, designated as rIII-11 (β3 274-368) and rIII-13 (β3 274-403), did not contain the established RGD-ligand binding sequence. In fact, they interacted, in a Ca2+-independent manner, with the C-terminal part of the fibrinogen gamma chain. Both β3 fragments blocked the participation of fibrinogen in the induction of platelet aggregation induced by adenosine diphosphate. Fragment rIII-13 was recognized by the anti-β3 monoclonal antibody B2A. This antibody, which possesses an epitope exposed on both resting and activated platelets, inhibited fibrinogen binding as well as platelet adhesion and aggregation. In conclusion, the results demonstrate that the 274-368 sequence of the β3 subunit of integrin αIIbβ3 constitutes a fibrinogen ligand binding domain, distinct from the RGD-binding site, that is required for both platelet adhesion and aggregation. © 1996 by The American Society of Hematology.