RGD INDUCES CONFORMATIONAL TRANSITION IN PURIFIED PLATELET INTEGRIN GPIIB IIIA-SDS SYSTEM YIELDING MULTIPLE BINDING STATES FOR FIBRINOGEN GAMMA-CHAIN C-TERMINAL PEPTIDE/

Fibrinogen gamma-chain C-terminal peptide HHLG-GAKQAGDV (gamma 12) and alpha-chain peptide GRGDSP are known to inhibit fibrinogen-mediated p latelet cell aggregation via competitive interactions with platelet in tegrin receptor GPIIb/IIIa. NMR studies of gamma 12 in the presence of purified GPIIb/IIIa in SDS/water solution have demonstrated the prese nce of two gamma 12 binding states, one of which is eliminated by GRGD SP (RGD) up to a RGD:gamma 12 ratio of 2:1. RGD:gamma 12 ratios greate r than 2:1 produce multiple sets of gamma 12 NMR signals in TOCSY spec tra. At a ratio of 4:1, two to four such resonance sets can be resolve d for A405, Q407, A408, G409, D410 and V411 spin systems. The number o f multiple resonances remains unchanged at ratios of 6:1 and 8:1. Addi tion of gamma 12 to reverse the ratio to 8:8 (1:1) has no apparent eff ect on the RGD-induced distribution. Results suggest that RGD irrevers ibly induces a conformational transition(s) in GPIIb/IIIa to produce m ultiple gamma 12 binding sites on the receptor.