The mechanism of inhibition of factor III (thromboplastin) activity by apolipoprotein B-100: Protein-protein interactions

Abstract

Factor III (thromboplastin) activity is inhibited by apoB-100, but the mechanism of inhibition is unknown. By examining the effect of purified apoB-100 can inhibit factor III via a different mechanism from that caused by the tissue-factor pathway inhibitor, which is mainly carried on the surface of lipoproteins. Although the presence of calcium ions and factors X and VII may enhance the rate o inhibition, they are not a prerequisite for the inhibition of factor III by apoB-100. In addition, by investigating the changes in the UV spectra of apoB-100 on interaction with factors X and VII and by assigning the shifts in absorption spectra to particular amino acids, we showed that these interactions involve negative and positive residuals within these proteins. By following the rates of interactions between apoB-100 and either factors III, X, or VII, a two-step mechanism, the primary interaction 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 analysis of the sequences of factor III revealed a possible binding site for apoB-100