Distinct Structural and Adhesive Roles of Ca2+ in Membrane Binding of Blood Coagulation Factors

Y. Zenmei Ohkubo, Emad Tajkhorshid

Research output: Contribution to journalArticlepeer-review

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 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 ω-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.

Original languageEnglish (US)
Pages (from-to)72-81
Number of pages10
JournalStructure
Volume16
Issue number1
DOIs
StatePublished - Jan 8 2008

Keywords

  • CELLBIO
  • PROTEINS

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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