The cofactor function of the N-terminal domain of tissue factor.

The Journal of Biological Chemistry
Farooqahmed S KitturAlireza R Rezaie

Abstract

Tissue factor (TF) is an integral membrane protein cofactor for factor VIIa (fVIIa) that initiates the blood coagulation cascade during vascular injury. TF has two fibrinonectin type III-like domains, both of which make extensive interactions with both the light and heavy chains of fVIIa. In addition to interaction with fVIIa, the membrane proximal C-terminal domain of TF is also known to bind the natural substrates factors IX and X, thereby facilitating their assembly and recognition by fVIIa in the activation complex. Both fVIIa and TF are elongated proteins, and their complex appears to be positioned nearly perpendicular to the membrane surface. It is possible that, similar to fVIIa, the N-terminal domain of TF also contacts the natural substrates. To investigate this possibility, we substituted all 23 basic and acidic residues of the N-terminal domain of TF with Ala or Asn and expressed the mutants as soluble TF(2-219) in a novel expression/purification vector system in the periplasmic space of bacteria. Following purification to homogeneity, the cofactor properties of mutants in promoting the amidolytic and proteolytic activity of fVIIa were analyzed in appropriate kinetic assays. The amidolytic activity assays indicated t...Continue Reading

References

Jan 1, 1980·Annual Review of Biochemistry·C M Jackson, Y Nemerson
Mar 28, 1998·The Journal of Biological Chemistry·G F Lee, R F Kelley
Oct 25, 2002·The Journal of Biological Chemistry·Likui YangAlireza R Rezaie

❮ Previous
Next ❯

Citations

Aug 19, 2007·Cell and Tissue Research·Chiaki HidaiShinichiro Kokubun
Jul 14, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Saulius ButenasKenneth G Mann
Jun 2, 2012·Frontiers in Bioscience (Landmark Edition)·Kanagasabai Vadivel, S Paul Bajaj
Sep 24, 2011·International Journal of Inflammation·Arthur J Chu
Feb 9, 2010·Thrombosis Research·Saulius ButenasKenneth G Mann
Jan 13, 2006·Biochemical and Biophysical Research Communications·Egon Persson
Dec 22, 2010·Biochimica Et Biophysica Acta·Jolanta Krudysz-AmbloSaulius Butenas
Jan 27, 2009·Biophysical Journal·Agnese S MinazzoJ B Alexander Ross
Jan 7, 2015·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Jana ProchazkovaMartin Prochazka

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.