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


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Z. Ohkubo Y. , Tajkhorshid E.

STRUCTURE, cilt.16, ss.72-81, 2008 (SCI İndekslerine Giren Dergi) identifier identifier

  • Cilt numarası: 16
  • Basım Tarihi: 2008
  • Doi Numarası: 10.1016/j.str.2007.10.021
  • Dergi Adı: STRUCTURE
  • Sayfa Sayısı: ss.72-81

Özet

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

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.