The connecting segment between both epidermal growth factor-like domains in blood coagulation factor IX contributes to stimulation by factor VIIIa and its isolated A2 domain.

The Journal of Biological Chemistry
Patrick H N CelieKoen Mertens

Abstract

The light chain of activated factor IX comprises multiple interactions between both epidermal growth factor-like domains that contribute to enzymatic activity and binding of factor IXa to its cofactor factor VIIIa. To investigate the association between factor IXa-specific properties and surface-exposed structure elements, chimeras were constructed in which the interconnection between the modules Leu(84)-Thr(87) and the factor IX-specific loop Asn(89)-Lys(91) were exchanged for corresponding regions of factor X and factor VII. In absence of factor VIIIa, all chimeras displayed normal enzymatic activity. In the presence of factor VIIIa, replacement of loop Asn(89)-Lys(91) resulted in a minor reduction in factor IXa activity. However, chimeras with substitutions or insertions in the spacer between the epidermal growth factor-like domains showed a major defect in response to factor VIIIa. Of these chimeras, some displayed a normal response to isolated factor VIII A2 domain as a cofactor in factor X activation. Surprisingly, chimeras containing elongated inter-domain spacers from factor X or VII displayed reduced response to both complete factor VIIIa and the isolated A2 domain. Moreover, these chimeras still displayed effective as...Continue Reading

References

May 20, 1988·Cell·B Furie, B C Furie
Nov 1, 1984·The Biochemical Journal·K MertensR M Bertina
Oct 10, 1995·Proceedings of the National Academy of Sciences of the United States of America·H BrandstetterW Bode
Nov 10, 1995·The Journal of Biological Chemistry·L M O'BrienP J Fay
Aug 5, 1993·Journal of Molecular Biology·K PadmanabhanW Kisiel
Jan 24, 1997·The Journal of Biological Chemistry·K A Lapan, P J Fay
Jul 21, 1998·The Journal of Biological Chemistry·P J Fay, K Koshibu
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·A C PikeE Persson

❮ Previous
Next ❯

Citations

Jan 30, 2003·Trends in Cardiovascular Medicine·Amy E Schmidt, S Paul Bajaj
Jan 19, 2007·Pathophysiology of Haemostasis and Thrombosis·Karin E KnobeRolf C R Ljung
Apr 14, 2009·Biological Chemistry·Thomas Zögg, Hans Brandstetter
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·L AutinB O Villoutreix
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·B Dahlbäck, B O Villoutreix
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·K E KnobeR C R Ljung
May 25, 2010·Journal of Thrombosis and Haemostasis : JTH·C N LinS W Lin
Mar 3, 2005·Journal of Molecular Biology·Marian Novotny, Gerard J Kleywegt
Dec 2, 2004·Blood Reviews·Philip J Fay, P Vincent Jenkins
Jan 21, 2004·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Jun 5, 2003·The Journal of Biological Chemistry·Mark D BlosteinBruce Furie

❮ 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.