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

Structure
Y Zenmei Ohkubo, Emad Tajkhorshid

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 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.

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Citations

Dec 10, 2013·The Journal of Physical Chemistry. B·Josh V Vermaas, Emad Tajkhorshid
May 13, 2011·The Journal of Biological Chemistry·Narjes TavoosiJames H Morrissey
Apr 14, 2009·Biological Chemistry·Thomas Zögg, Hans Brandstetter
Jan 24, 2016·Protein Expression and Purification·Aline de Sousa BomfimElisa Maria de Sousa Russo
Mar 16, 2012·Thrombosis Research·James H MorrisseyChad M Rienstra
Mar 27, 2012·Thrombosis Research·Maureane Hoffman
Mar 2, 2010·Thrombosis Research·Maureane Hoffman, Dougald M Monroe
Feb 5, 2010·Thrombosis Research·James H MorrisseyEmad Tajkhorshid
Jan 24, 2014·The Journal of Physical Chemistry. B·Taras V PogorelovEmad Tajkhorshid
May 13, 2011·The Journal of Physical Chemistry. B·Mark J ArcarioEmad Tajkhorshid
Sep 15, 2009·Journal of Molecular Biology·James GumbartEmad Tajkhorshid
Jan 13, 2009·Thrombosis Research·Ouerdia ChafaBernard F LeBonniec
Mar 25, 2008·Biophysical Journal·Jiankuai Diao, Emad Tajkhorshid
Nov 29, 2013·Thrombosis and Haemostasis·Narjes Tavoosi, James H Morrissey
Jul 28, 2009·Journal of Thrombosis and Haemostasis : JTH·J H MorrisseyE Tajkhorshid
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Jul 25, 2012·Biophysical Journal·Y Zenmei OhkuboEmad Tajkhorshid
Oct 11, 2012·Journal of Chemical Theory and Computation·David E TannerKlaus Schulten
Mar 1, 2017·The Journal of Physical Chemistry. B·Josh V VermaasEmad Tajkhorshid
Sep 1, 2012·Global Advances in Health and Medicine : Improving Healthcare Outcomes Worldwide·Kara FitzgeraldKathie Swift
Aug 7, 2017·Journal of Thrombosis and Haemostasis : JTH·M P MullerE Tajkhorshid
Nov 26, 2019·Journal of Computational Chemistry·Shashank Pant, Emad Tajkhorshid
Aug 23, 2018·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Bushra Husain, Diego Ellerman
Mar 7, 2021·Journal of Clinical Medicine·Alessandro AliottaLorenzo Alberio
Feb 8, 2011·Biochemistry·John M BoettcherChad M Rienstra
Aug 12, 2008·Thrombosis Research·James H MorrisseyEmad Tajkhorshid

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