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

Kevin H. Mayo, Francis Fan, Mary Pat Beavers, Annette Eckardt, Patricia Keane, William J. Hoekstra, Patricia Andrade-Gordon

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Fibrinogen γ-chain C-terminal peptide HHLG-GAKQAGDV (γ12) and γ-chain peptide GRGDSP are known to inhibit fibrinogen-mediated platelet cell aggregation via competitive interactions with platelet integrin receptor GPIIb/lIIa. NMR studies of γ12 in the presence of purified GPIlb/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: γ12 ratios greater than 2:1 produce multiple sets of γ12 NMR signals in TOCSY pectra. At a ratio of 4:1, tw 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.

Original languageEnglish (US)
Pages (from-to)79-82
Number of pages4
JournalFEBS Letters
Volume378
Issue number1
DOIs
StatePublished - Jan 2 1996

Bibliographical note

Funding Information:
Acknowledgements: This work benefitted from research grants from the W. W. Smith Charitable Trust, Philadelphia, PA, and from the R. W. Johnson Pharmaceutical Research Institute, Springhouse. PA. We are very grateful to Eric Eccleston and Denisha Walik of the Department of Human Genetics Microchemical Facility, University of Minnesota for the synthesis of peptides used in this study. The authors also would like to thank Jeff Press for his support for this project.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Fibrinogen
  • Integrin GPIIb/IIIa
  • NMR spectroscopy
  • Peptide
  • Platelet

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