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Modeling of annexin A2—Membrane interactions by molecular dynamics simulations

The annexins are a family of Ca(2+)-regulated phospholipid binding proteins that are involved in membrane domain organization and membrane trafficking. Although they are widely studied and crystal structures are available for several soluble annexins their mode of membrane association has never been...

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Autores principales: Hakobyan, Davit, Gerke, Volker, Heuer, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609761/
https://www.ncbi.nlm.nih.gov/pubmed/28937994
http://dx.doi.org/10.1371/journal.pone.0185440
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author Hakobyan, Davit
Gerke, Volker
Heuer, Andreas
author_facet Hakobyan, Davit
Gerke, Volker
Heuer, Andreas
author_sort Hakobyan, Davit
collection PubMed
description The annexins are a family of Ca(2+)-regulated phospholipid binding proteins that are involved in membrane domain organization and membrane trafficking. Although they are widely studied and crystal structures are available for several soluble annexins their mode of membrane association has never been studied at the molecular level. Here we obtained molecular information on the annexin-membrane interaction that could serve as paradigm for the peripheral membrane association of cytosolic proteins by Molecular Dynamics simulations. We analyzed systems containing the monomeric annexin A2 (AnxA2), a membrane with negatively charged phosphatidylserine (POPS) lipids as well as Ca(2+) ions. On the atomic level we identify the AnxA2 orientations and the respective residues which display the strongest interaction with Ca(2+) ions and the membrane. The simulation results fully agree with earlier experimental findings concerning the positioning of bound Ca(2+) ions. Furthermore, we identify for the first time a significant interaction between lysine residues of the protein and POPS lipids that occurs independently of Ca(2+) suggesting that AnxA2-membrane interactions can also occur in a low Ca(2+) environment. Finally, by varying Ca(2+) concentrations and lipid composition in our simulations we observe a calcium-induced negative curvature of the membrane as well as an AnxA2-induced lipid ordering.
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spelling pubmed-56097612017-10-09 Modeling of annexin A2—Membrane interactions by molecular dynamics simulations Hakobyan, Davit Gerke, Volker Heuer, Andreas PLoS One Research Article The annexins are a family of Ca(2+)-regulated phospholipid binding proteins that are involved in membrane domain organization and membrane trafficking. Although they are widely studied and crystal structures are available for several soluble annexins their mode of membrane association has never been studied at the molecular level. Here we obtained molecular information on the annexin-membrane interaction that could serve as paradigm for the peripheral membrane association of cytosolic proteins by Molecular Dynamics simulations. We analyzed systems containing the monomeric annexin A2 (AnxA2), a membrane with negatively charged phosphatidylserine (POPS) lipids as well as Ca(2+) ions. On the atomic level we identify the AnxA2 orientations and the respective residues which display the strongest interaction with Ca(2+) ions and the membrane. The simulation results fully agree with earlier experimental findings concerning the positioning of bound Ca(2+) ions. Furthermore, we identify for the first time a significant interaction between lysine residues of the protein and POPS lipids that occurs independently of Ca(2+) suggesting that AnxA2-membrane interactions can also occur in a low Ca(2+) environment. Finally, by varying Ca(2+) concentrations and lipid composition in our simulations we observe a calcium-induced negative curvature of the membrane as well as an AnxA2-induced lipid ordering. Public Library of Science 2017-09-22 /pmc/articles/PMC5609761/ /pubmed/28937994 http://dx.doi.org/10.1371/journal.pone.0185440 Text en © 2017 Hakobyan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hakobyan, Davit
Gerke, Volker
Heuer, Andreas
Modeling of annexin A2—Membrane interactions by molecular dynamics simulations
title Modeling of annexin A2—Membrane interactions by molecular dynamics simulations
title_full Modeling of annexin A2—Membrane interactions by molecular dynamics simulations
title_fullStr Modeling of annexin A2—Membrane interactions by molecular dynamics simulations
title_full_unstemmed Modeling of annexin A2—Membrane interactions by molecular dynamics simulations
title_short Modeling of annexin A2—Membrane interactions by molecular dynamics simulations
title_sort modeling of annexin a2—membrane interactions by molecular dynamics simulations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609761/
https://www.ncbi.nlm.nih.gov/pubmed/28937994
http://dx.doi.org/10.1371/journal.pone.0185440
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