The apolipoprotein B3304-3317 peptide as an inhibitor of the lipoprotein (a):apolipoprotein B-containing lipoprotein interaction.
Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease. It is characterized by apolipoprotein (a) [apo(a)] disulphide linked to apolipoprotein B (apoB), by Cys4057 of apo(a) and possibly Cys3734 of apoB. We call this the covalent apo(a):apoB-Lp interaction, to distinguish it from the non-covalent Lp(a):apoB-Lp interaction, mediated by the proline-binding kringle-4-like domain(s) of Lp(a). The Lp(a):apoB-Lp interaction was inhibited by an apoB peptide spanning residues 3304-3317. This peptide was found by a computerized search for sites on apoB similar to the plasminogen's kringle-4-binding site of alpha 2-antiplasmin. It probably constitutes part of the Lp(a)-binding site on apoB because: (1) it corresponds to the alpha 2-antiplasmin minimum binding domain for plasminogen's kringle-4; (2) the competitive nature of inhibition [KI = (1.5 +/- 0.7) x 10(-4) M, n = 5] suggested that it and apoB-Lp bound to Lp(a) by the same mechanism at the same site; and (3) it specifically bound Lp(a) and not apoB-Lp, and the bound Lp(a) was dissociated by inhibitors of the Lp(a):apoB-Lp interaction, 6-aminohexanoic acid and L-proline. Inhibition was independent of its proline residue, suggesting that proline in the context of a peptide is not a ligand for the kringle(s) which mediated the binding of Lp(a) to apoB-Lp.
Trieu
V N
VN
Department of Medicine, University of North Texas Health Science Center at Fort Worth 76107, USA.
Olsson
U
U
McConathy
W J
WJ
D000595:Amino Acid Sequence; D001055:Apolipoproteins B / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001665:Binding Sites; D001667:Binding, Competitive; D002846:Chromatography, Affinity; D003864:Depression, Chemical; D006801:Humans; D005779:Immunodiffusion; D018082:Kringles; D017270:Lipoprotein(a) / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D011392:Proline / Q000737:chemistry; D011485:Protein Binding / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000979:alpha-2-Antiplasmin / Q000737:chemistry
D001055:Apolipoproteins B; D017270:Lipoprotein(a); D010446:Peptide Fragments; D011994:Recombinant Proteins; D000979:alpha-2-Antiplasmin; C093007:apolipoprotein B (3304-3317); D011392:Proline