CONFORMATIONAL-CHANGES IN FIBRINOGEN ELICITED BY ITS INTERACTION WITHPLATELET MEMBRANE GLYCOPROTEIN-GPIIB-IIIA

The binding of fibrinogen to membrane glycoprotein GPIIb-IIIa on activ ated platelets leads to platelet aggregation. This interaction results in conformational changes in fibrinogen as evidenced by the expressio n of receptor-induced binding sites, RIBS, epitopes which are expresse d by the bound but not the free ligand. In the present study, two RIBS epitopes have been localized. One sequence resides at gamma112-119 an d is recognized by mAb 9F9; the second is the RGDF sequence at Aalpha 95-98 and is recognized by mAb 155B16. These epitopes are also exposed by adsorption of fibrinogen onto a plastic surface and digestion of t he molecule by plasmin. Proteolytic exposure of the epitopes coincides with cleavage of the carboxyl-terminal aspects of the Aalpha-chains t o form fragment X2. The inaccessibility of the RGDF sequence at Aalpha 95-98 in fibrinogen suggests that this sequence does not participate in the initial binding of the molecule to GPII-bIIIa. The location of these RIBS epitopes suggests a model in which binding of fibrinogen to its receptor alters the conformation of the carboxyl-terminal aspects of the Aalpha-chains, exposing the sequences which reside in the coil ed-coil connector segments between the D and E domains of the molecule . These sequences may then serve as epitopes and may mediate unique fu nctions of the receptor-bound molecule.