Role of fibrinogen α and γ chain sites in platelet aggregation

Fibrinogen (Fbg) mediates platelet aggregation by its interaction with the platelet glycoprotein IIb-IIIa (integrin α(IIb)β₃). Peptides containing the amino acid sequence RGD derived from the α chain (residues α95-97 and residues α572-574) and the sequence HHLGGAKQAGDV derived from the carboxyl terminus of the γ chain of Fbg (residues γ400-411) inhibit these interactions. To determine the role of these sequences in intact Fbg, recombinant human Fbg (rFbg), mutant rFbgs with an RGD → RGE substitution at either position α97 or α574, and a rFbg γ'-containing variant that has a carboxyl-terminal interruption in the HHLGGAKQAGDV sequence have been expressed in transfected BHK cells. Purified rFbg and the two RGE mutant Fbgs were similar to plasma Fbg in platelet aggregation assays. In contrast, the γ' variant Fbg was markedly defective in platelet aggregation. These data support the proposals that the carboxyl-terminal region of the γ chain of Fbg is essential for optimal platelet aggregation and that the α-chain RGD sequences are neither necessary nor sufficient for platelet aggregation.