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Molecular Determinants of Phospholipid Synergy in Blood Clotting
Many regulatory processes in biology involve reversible association of proteins with membranes. Clotting proteins bind to phosphatidylserine (PS) on cell surfaces, but a clear picture of this interaction has yet to emerge. We present a novel explanation for membrane binding by GLA domains of clottin...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123091/ https://www.ncbi.nlm.nih.gov/pubmed/21561861 http://dx.doi.org/10.1074/jbc.M111.251769 |
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author | Tavoosi, Narjes Davis-Harrison, Rebecca L. Pogorelov, Taras V. Ohkubo, Y. Zenmei Arcario, Mark J. Clay, Mary C. Rienstra, Chad M. Tajkhorshid, Emad Morrissey, James H. |
author_facet | Tavoosi, Narjes Davis-Harrison, Rebecca L. Pogorelov, Taras V. Ohkubo, Y. Zenmei Arcario, Mark J. Clay, Mary C. Rienstra, Chad M. Tajkhorshid, Emad Morrissey, James H. |
author_sort | Tavoosi, Narjes |
collection | PubMed |
description | Many regulatory processes in biology involve reversible association of proteins with membranes. Clotting proteins bind to phosphatidylserine (PS) on cell surfaces, but a clear picture of this interaction has yet to emerge. We present a novel explanation for membrane binding by GLA domains of clotting proteins, supported by biochemical studies, solid-state NMR analyses, and molecular dynamics simulations. The model invokes a single “phospho-l-serine-specific” interaction and multiple “phosphate-specific” interactions. In the latter, the phosphates in phospholipids interact with tightly bound Ca(2+) in GLA domains. We show that phospholipids with any headgroup other than choline strongly synergize with PS to enhance factor X activation. We propose that phosphatidylcholine and sphingomyelin (the major external phospholipids of healthy cells) are anticoagulant primarily because their bulky choline headgroups sterically hinder access to their phosphates. Following cell damage or activation, exposed PS and phosphatidylethanolamine collaborate to bind GLA domains by providing phospho-l-serine-specific and phosphate-specific interactions, respectively. |
format | Online Article Text |
id | pubmed-3123091 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-31230912011-06-30 Molecular Determinants of Phospholipid Synergy in Blood Clotting Tavoosi, Narjes Davis-Harrison, Rebecca L. Pogorelov, Taras V. Ohkubo, Y. Zenmei Arcario, Mark J. Clay, Mary C. Rienstra, Chad M. Tajkhorshid, Emad Morrissey, James H. J Biol Chem Membrane Biology Many regulatory processes in biology involve reversible association of proteins with membranes. Clotting proteins bind to phosphatidylserine (PS) on cell surfaces, but a clear picture of this interaction has yet to emerge. We present a novel explanation for membrane binding by GLA domains of clotting proteins, supported by biochemical studies, solid-state NMR analyses, and molecular dynamics simulations. The model invokes a single “phospho-l-serine-specific” interaction and multiple “phosphate-specific” interactions. In the latter, the phosphates in phospholipids interact with tightly bound Ca(2+) in GLA domains. We show that phospholipids with any headgroup other than choline strongly synergize with PS to enhance factor X activation. We propose that phosphatidylcholine and sphingomyelin (the major external phospholipids of healthy cells) are anticoagulant primarily because their bulky choline headgroups sterically hinder access to their phosphates. Following cell damage or activation, exposed PS and phosphatidylethanolamine collaborate to bind GLA domains by providing phospho-l-serine-specific and phosphate-specific interactions, respectively. American Society for Biochemistry and Molecular Biology 2011-07-01 2011-05-11 /pmc/articles/PMC3123091/ /pubmed/21561861 http://dx.doi.org/10.1074/jbc.M111.251769 Text en © 2011 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles |
spellingShingle | Membrane Biology Tavoosi, Narjes Davis-Harrison, Rebecca L. Pogorelov, Taras V. Ohkubo, Y. Zenmei Arcario, Mark J. Clay, Mary C. Rienstra, Chad M. Tajkhorshid, Emad Morrissey, James H. Molecular Determinants of Phospholipid Synergy in Blood Clotting |
title | Molecular Determinants of Phospholipid Synergy in Blood Clotting |
title_full | Molecular Determinants of Phospholipid Synergy in Blood Clotting |
title_fullStr | Molecular Determinants of Phospholipid Synergy in Blood Clotting |
title_full_unstemmed | Molecular Determinants of Phospholipid Synergy in Blood Clotting |
title_short | Molecular Determinants of Phospholipid Synergy in Blood Clotting |
title_sort | molecular determinants of phospholipid synergy in blood clotting |
topic | Membrane Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123091/ https://www.ncbi.nlm.nih.gov/pubmed/21561861 http://dx.doi.org/10.1074/jbc.M111.251769 |
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