TCB Publications - Abstract

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$^{2+}$-dependent manner. However, the critical role of Ca$^{2+}$ 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 $\omega$-loop into the membrane and direct interactions of structurally bound Ca$^{2+}$ ions and protein side chains with negative lipids. The model suggests that Ca$^{2+}$ ions play two distinct roles in the process: the four inner Ca$^{2+}$ ions are primarily responsible for an optimal folding of the GLA domain for membrane insertion, whereas the outer Ca$^{2+}$ ions anchor the protein to the membrane through direct contacts with lipids.

Request Full Text

Request Paper

Full Name
Email Address
Type the number eight in the box