Distinct structural and adhesive roles of Ca2+ in membrane binding of blood coagulation factors


Creative Commons License

Z. Ohkubo Y. , Tajkhorshid E.

STRUCTURE, vol.16, pp.72-81, 2008 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 16
  • Publication Date: 2008
  • Doi Number: 10.1016/j.str.2007.10.021
  • Title of Journal : STRUCTURE
  • Page Numbers: pp.72-81

Abstract

The GLA domain, a common membrane-anchoring domain of several serine protease coagulation factors, is a key element in membrane association and activation of these factors in a highly Ca2+-dependent manner. However, the critical role of Ca2+ ions in binding is only poorly understood. Here, we present the atomic model of a membrane-bound GLA domain by using MID simulations of the GLA domain of human factor Vila and an anionic lipid bilayer. The binding is furnished through a complete insertion of the omega-loop into the membrane and through direct interactions of structurally bound Ca2+ ions and protein side chains with negative lipids. The model suggests that Ca2+ ions play two distinct roles in the process: the four inner Ca2+ ions are primarily responsible for optimal folding of the GLA domain for membrane insertion, whereas the outer Ca2+ ions anchor the protein to the membrane through direct contacts with lipids.

Distinct structural and adhesive roles of Ca2+ in membrane binding of blood coagulation factors