C. Ettelaie et al., ALTERATIONS IN THE STRUCTURE OF APOLIPOPROTEIN B-100 DETERMINE THE BEHAVIOR OF LDL TOWARDS THROMBOPLASTIN, Biochimica et biophysica acta, L. Lipids and lipid metabolism, 1345(3), 1997, pp. 237-247
Apolipoprotein B-100 acts as an inhibitor of thromboplastin activity i
ndependently of the tissue factor pathway inhibitor (TFPI) associated
with plasma lipoproteins. Analysis of the primary structure of Apo B-1
00 showed a higher than expected occurrence of lysine groups in the re
ceptor-binding region. In order to demonstrate the participation of ly
sine groups of Apo B-100 in the inhibition of thromboplastin, thrombop
lastin and Apo B-100 were incubated together in the presence of poly-L
-lysine, poly-L-arginine, lysine and arginine monomers. The inhibition
of thromboplastin by Apo B-100 was completely suppressed in the prese
nce of poly-L-lysine. Poly-L-arginine was found to be less effective a
nd neither lysine or arginine monomers had any significant effect on t
he inhibitory effect of Apo B-100. Alterations in the structure of Apo
B-100 reconstituted in lipid vesicles resembling LDL, brought about b
y lipid peroxidation and lipid loading were examined by means of Fouri
er transform infra-red spectroscopy. It was found that, upon oxidation
without the addition of cupric ions, the apolipoprotein attains a mor
e exposed conformation with an increase in alpha-helical structure. Th
is increase occurred at the expense of beta-structure. On lipid loadin
g, an increase in beta-structure at the expense of the alpha-helix, wa
s demonstrated. It is therefore proposed that the variable action of L
DL towards thromboplastin derives from alterations in the secondary st
ructure of the Apo B-100, particularly the receptor-binding region.