Interaction of β3 integrin-derived peptides 214-218 and 217-231 with α(IIb)β3 complex and with fibrinogen Aα-chain

Iwona Wierzbicka, M. Anna Kowalska, Elizabeth C. Lasz, David Farrell, Andrei Z. Budzynski, Stefan Niewiarowski

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

β3 integrin-derived peptides 214-218 and 217-231 have been shown previously to inhibit platelet aggregation and fibrinogen binding to platelets and to purified receptor. In this paper we study the activity of both peptides in inhibition of binding of biotinylated fibrinogen to activated platelets and to immobilized α(IIb)β3 receptor. We found that the mechanism of this inhibition by both peptides is different. 125I-labeled 214-218 peptide binds to α(IIb)β3 but in contrast, 125I-labeled 217-231 peptide binds to the Aα-chain of native and γ' fibrinogen, as judged by the cross-linking study. In solid phase assay both purified α(IIb)β3 and 217-231 peptide bound extensively to native and recombinant fibrinogen, and to fibrinogen with either D574E or D97E mutations in the Aα-chain. Binding of purified α(IIb)β3 to γ' fibrinogen was markedly impaired whereas binding of 217-231 was only slightly impaired in comparison with native fibrinogen. Binding of 217-231 to fibrinogen fragment X was also reduced suggesting that sequences other than RGDS and RGDF may represent binding sites for this peptide. We hypothesize that the close vicinity of fibrinogen binding site (217-231) and of the site participating in conformational changes of the α(IIb)β3 receptor (214-218) may facilitate fibrinogen interaction with its receptor.

Original languageEnglish (US)
Pages (from-to)115-126
Number of pages12
JournalThrombosis Research
Volume85
Issue number2
DOIs
StatePublished - Jan 15 1997
Externally publishedYes

Fingerprint

Integrins
Fibrinogen
Peptides
Blood Platelets
Binding Sites
Platelet Aggregation
Mutation

Keywords

  • α(IIb)β integrin
  • β-derived peptides
  • fibrinogen
  • fibrinogen variants
  • platelets

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Hematology

Cite this

Interaction of β3 integrin-derived peptides 214-218 and 217-231 with α(IIb)β3 complex and with fibrinogen Aα-chain. / Wierzbicka, Iwona; Kowalska, M. Anna; Lasz, Elizabeth C.; Farrell, David; Budzynski, Andrei Z.; Niewiarowski, Stefan.

In: Thrombosis Research, Vol. 85, No. 2, 15.01.1997, p. 115-126.

Research output: Contribution to journalArticle

Wierzbicka, Iwona ; Kowalska, M. Anna ; Lasz, Elizabeth C. ; Farrell, David ; Budzynski, Andrei Z. ; Niewiarowski, Stefan. / Interaction of β3 integrin-derived peptides 214-218 and 217-231 with α(IIb)β3 complex and with fibrinogen Aα-chain. In: Thrombosis Research. 1997 ; Vol. 85, No. 2. pp. 115-126.
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