Y. Zenmei Ohkubo and Emad Tajkhorshid.
Distinct structural and adhesive roles of Ca2+ in membrane
binding of blood coagulation factors.
Structure, 16:72-81, 2008.
OHKU2008-ET
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 Ca-dependent manner. However, the critical role of Ca ions in binding is only poorly understood. Here, we present a first atomic model of a membrane-bound GLA domain using MD simulations of the GLA domain of human factor VIIa and an anionic lipid bilayer. The binding is furnished through a complete insertion of the -loop into the membrane and direct interactions of structurally bound Ca ions and protein side chains with negative lipids. The model suggests
that Ca ions play two distinct roles in the process: the four inner Ca ions are primarily responsible for an optimal folding of the GLA domain for membrane insertion, whereas the outer Ca ions anchor the protein to the membrane through direct contacts with lipids.