C. Ettelaie et al., THE MECHANISM OF INHIBITION OF FACTOR-III (THROMBOPLASTIN) ACTIVITY BY APOLIPOPROTEIN-B-100 - PROTEIN-PROTEIN INTERACTIONS, Arteriosclerosis, thrombosis, and vascular biology, 16(5), 1996, pp. 639-647
Factor III (thromboplastin) activity is inhibited by apoB-100, but the
mechanism of inhibition is unknown. By examining the effect of purifi
ed apoB-100 on factor III activity, we showed that apoB-100 can inhibi
t factor III via a different mechanism from that caused by the tissue-
factor pathway-inhibitor, which is mainly carried on the surface of li
poproteins. Although the presence of calcium ions and factors X and VI
I may enhance the rate of inhibition, they are not a prerequisite for
the inhibition of factor III by apoB-100. In addition, by investigatin
g the changes in the UV spectra of apoB-100 on interaction with factor
III and factors X and VII and by assigning the shifts in absorption s
pectra to particular amino acids, we showed that these interactions in
volve negative and positive residues within these proteins. By followi
ng the rates of interactions between apoB-100 and either factors III,
X, or VII, a two-step mechanism for the inhibition process involving f
actors X and VII was postulated. In this mechanism, the primary intera
ction of apoB-100 with factor III is followed by a rate-limiting step
that can be accelerated by the presence of either factor X or VII and
leads to the inhibition of factor III. Furthermore, a computer-based a
nalysis of the sequences of factor III revealed a possible binding sit
e for apoB-100.