Interaction of beta 3 integrin-derived peptides 214-218 and 217-231 with alpha IIb beta 3 complex and with fibrinogen A alpha-chain.
beta 3 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 alpha IIb beta 3 receptor. We found that the mechanism of this inhibition by both peptides is different 125I-labeled 214-218 peptide binds to alpha IIb beta 3 but in contrast, 125I-labeled 217-231 peptide binds to the A alpha-chain of native and gamma' fibrinogen, as judged by the cross-linking study. In solid phase assay both purified alpha IIb beta 3 and 217-231 peptide bound extensively to native and recombinant fibrinogen, and to fibrinogen with either D574E or D97E mutations in the A alpha-chain. Binding of purified alpha IIb beta 3 to gamma' 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 alpha IIb beta 3 receptor (214-218) may facilitate fibrinogen interaction with its receptor.
Wierzbicka
I
I
Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Kowalska
M A
MA
Lasz
E C
EC
Farrell
D H
DH
Budzynski
A Z
AZ
Niewiarowski
S
S
D000244:Adenosine Diphosphate / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D039661:Integrin beta3; D016023:Integrins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*
D015703:Antigens, CD; D039661:Integrin beta3; D016023:Integrins; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D000244:Adenosine Diphosphate; D005340:Fibrinogen