This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ettelaie, C. Articles by Bruckdorfer, K. R. Search for Related Content PubMed PubMed Citation Articles by Ettelaie, C. Articles by Bruckdorfer, K. R.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:639-647.)
© 1996 American Heart Association, Inc.

Articles

The Mechanism of Inhibition of Factor III (Thromboplastin) Activity by Apolipoprotein B-100

Protein-Protein Interactions

Camille Ettelaie; Nicola J. James; Barry Wilbourn; Jacqueline M. Adam; Khalid M. Naseem; K. Richard Bruckdorfer

From the Department of Biochemistry and Molecular Biology, Royal Free Hospital School of Medicine, London, UK.

Correspondence to Camille Ettelaie, Department of Biochemistry and Molecular Biology, Royal Free Hospital School of Medicine, Rowland Hill St, London, UK, NW3 2PF. E-mail camille@rfhsm.ac.uk.

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 on factor III activity, we showed that 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 of 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 factor III and 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 residues within these proteins. By following the rates of interactions between apoB-100 and either factors III, X, or VII, a two-step mechanism for the inhibition process involving factors X and VII was postulated. In this 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.

Key Words: apolipoprotein B-100 • factor III (thromboplastin) • factor VII • factor X • UV spectroscopy

This article has been cited by other articles:

				C. Ettelaie, B. R. Wilbourn, J. M. Adam, N. J. James, and K. R. Bruckdorfer Comparison of the Inhibitory Effects of ApoB100 and Tissue Factor Pathway Inhibitor on Tissue Factor and the Influence of Lipoprotein Oxidation Arterioscler Thromb Vasc Biol, July 1, 1999; 19(7): 1784 - 1790. [Abstract] [Full Text] [PDF]

				M. P. Moyer, R. P. Tracy, P. B. Tracy, C. v.'t Veer, C. E. Sparks, and K. G. Mann Plasma Lipoproteins Support Prothrombinase and Other Procoagulant Enzymatic Complexes Arterioscler Thromb Vasc Biol, March 1, 1998; 18(3): 458 - 465. [Abstract] [Full Text] [PDF]