Binding of recombinant apolipoprotein(a) to extracellular matrix proteins.
Elevated levels of lipoprotein(a), which consists of apolipoprotein(a) [apo(a)] covalently linked to a low-density lipoprotein-like moiety, is an independent risk factor for the development of atherosclerosis. We show that a recombinant form of apo(a) [r-apo(a)] binds strongly to fibronectin and fibrinogen, weakly to laminin, and not at all to von Willebrand factor, vitronectin, or collagen type IV. In contrast to the binding of plasminogen to fibronectin, r-apo(a) binding does not appear to be mediated by lysine-dependent interactions, based on the inability of epsilon-aminocaproic acid concentrations up to 0.2 mol/L to significantly decrease r-apo(a) binding to fibronectin. Plasminogen competed weakly for the binding of r-apo(a) to fibronectin, whereas r-apo(a) completely abolished plasminogen binding. The 29- and 38-kd heparin-binding thermolysin fragments of fibronectin, previously identified as the lipoprotein(a) binding domains, were digested with trypsin, and a peptide that retained the ability to bind r-apo(a) was isolated; the sequence of the peptide (AVTTIPAPTDLK) corresponds to the amino terminus of the 29- and 38-kd domains. A synthetic peptide with this sequence was able to compete effectively with fibronectin for r-apo(a) binding.
van der Hoek
Y Y
YY
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
Sangrar
W
W
Côté
G P
GP
Kastelein
J J
JJ
Koschinsky
M L
ML
D000614:Aminocaproates / Q000494:pharmacology; D001054:Apolipoproteins A / Q000378:metabolism*; D001667:Binding, Competitive; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D011994:Recombinant Proteins
D000614:Aminocaproates; D001054:Apolipoproteins A; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D010958:Plasminogen