RGD induces conformational transition in purified platelet integrin GPIIb/IIIa‐SDS system yielding multiple binding states for fibrinogen γ‐chain C‐terminal peptide

FEBS Letters

Eckardt, Annette¹  Fan, Francis²  Andrade-Gordon, Patricia¹  Beavers, Mary Pat¹  Hoekstra, William J.¹  Keane, Patricia¹  Mayo, Kevin H.² 

[1] The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477, USA;Department of Biochemistry, Biomedical Engineering Center, University of Minnesota, 420 Delaware STreet, S. E., Minneapolis, MN 55455, USA

关键词: Fibrinogen;    Peptide;    Platelet;    Integrin GPIIb/IIla;    NMR spectroscopy;    NMR;    nuclear magnetic resonance;    2D-NMR;    two-dimensional NMR spectroscopy;    HOHAHA;    2D-NMR homonuclear Hartman-Hahn spectroscopy;    NOE;    nuclear Overhauser effect;    NOESY;    2D-NMR nuclear Overhauser effect spectroscopy;    rf;    radio frequency;    FID;    free induction decay;    GP;    glycoprotein;    GPIIb/IIIa;    integrin receptor GPαIIbβ 3;    SDS;    sodium dodecyl sulfate;    γ12;    dodecapeptide HHLGGAKQAGDV;    derived from the fibrinogen γ-chain C-terminus;    RGD;    hexapeptide GSP;   

DOI  :  10.1016/0014-5793(95)01418-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown