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RGD induces conformational transition in purified platelet integrin GPIIb/IIIa‐SDS system yielding multiple binding states for fibrinogen γ‐chain C‐terminal peptide
Author(s) -
Mayo Kevin H.,
Fan Francis,
Beavers Mary Pat,
Eckardt Annette,
Keane Patricia,
Hoekstra William J.,
Andrade-Gordon Patricia
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01418-7
Subject(s) - fibrinogen , integrin , chemistry , peptide , platelet , binding site , platelet activation , receptor , microbiology and biotechnology , biophysics , biochemistry , biology , immunology
Fibrinogen γ‐chain C‐terminal peptide HHLGGAKQAGDV (γ12) and α‐chain peptide GRGDSP are known to inhibit fibrinogen‐mediated platelet cell aggregation via competitive interactions with platelet integrin receptor GPIlb/IIIa. NMR studies of γ12 in the presence of purified GPIIb/IIIa in SDS/water solution have demonstrated the presence of two γ12 binding states, one of which is eliminated by GRGDSP (RGD) up to a RGD: γ12 ratio of 2:1. RGD: γl2 ratios greater than 2:1 produce multiple sets of γ12 NMR signals in TOCSY spectra. At a ratio of 4:1, two to four such resonance sets can be resolved for A405, Q407, A408, G409, D410 and V411 spin systems. The number of multiple resonances remains unchanged at ratios of 6:1 and 8:1. Addition of γ12 to reverse the ratio to 8:8 (1::1) has no apparent effect on the RGD‐induced distribution. Results suggest that RGD irreversibly induces a conformational transition(s) in GPIIb/IIIa to produce multiple γ12 binding sites on the receptor.