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Interactions of Pleckstrin Homology Domains with Membranes: Adding Back the Bilayer via High-Throughput Molecular Dynamics
A molecular simulation pipeline for determining the mode of interaction of pleckstrin homology (PH) domains with phosphatidylinositol phosphate (PIP)-containing lipid bilayers is presented. We evaluate our methodology for the GRP1 PH domain via comparison with structural and biophysical data. Coarse...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975593/ https://www.ncbi.nlm.nih.gov/pubmed/27427480 http://dx.doi.org/10.1016/j.str.2016.06.002 |
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author | Yamamoto, Eiji Kalli, Antreas C. Yasuoka, Kenji Sansom, Mark S.P. |
author_facet | Yamamoto, Eiji Kalli, Antreas C. Yasuoka, Kenji Sansom, Mark S.P. |
author_sort | Yamamoto, Eiji |
collection | PubMed |
description | A molecular simulation pipeline for determining the mode of interaction of pleckstrin homology (PH) domains with phosphatidylinositol phosphate (PIP)-containing lipid bilayers is presented. We evaluate our methodology for the GRP1 PH domain via comparison with structural and biophysical data. Coarse-grained simulations yield a 2D density landscape for PH/membrane interactions alongside residue contact profiles. Predictions of the membrane localization and interactions of 13 PH domains reveal canonical, non-canonical, and dual PIP-binding sites on the proteins. Thus, the PH domains associate with the PIP molecules in the membrane via a highly positively charged loop. Some PH domains exhibit modes of interaction with PIP-containing membranes additional to this canonical binding mode. All 13 PH domains cause a degree of local clustering of PIP molecules upon binding to the membrane. This provides a global picture of PH domain interactions with membranes. The high-throughput approach could be extended to other families of peripheral membrane proteins. |
format | Online Article Text |
id | pubmed-4975593 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49755932016-08-11 Interactions of Pleckstrin Homology Domains with Membranes: Adding Back the Bilayer via High-Throughput Molecular Dynamics Yamamoto, Eiji Kalli, Antreas C. Yasuoka, Kenji Sansom, Mark S.P. Structure Theory A molecular simulation pipeline for determining the mode of interaction of pleckstrin homology (PH) domains with phosphatidylinositol phosphate (PIP)-containing lipid bilayers is presented. We evaluate our methodology for the GRP1 PH domain via comparison with structural and biophysical data. Coarse-grained simulations yield a 2D density landscape for PH/membrane interactions alongside residue contact profiles. Predictions of the membrane localization and interactions of 13 PH domains reveal canonical, non-canonical, and dual PIP-binding sites on the proteins. Thus, the PH domains associate with the PIP molecules in the membrane via a highly positively charged loop. Some PH domains exhibit modes of interaction with PIP-containing membranes additional to this canonical binding mode. All 13 PH domains cause a degree of local clustering of PIP molecules upon binding to the membrane. This provides a global picture of PH domain interactions with membranes. The high-throughput approach could be extended to other families of peripheral membrane proteins. Cell Press 2016-08-02 /pmc/articles/PMC4975593/ /pubmed/27427480 http://dx.doi.org/10.1016/j.str.2016.06.002 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Theory Yamamoto, Eiji Kalli, Antreas C. Yasuoka, Kenji Sansom, Mark S.P. Interactions of Pleckstrin Homology Domains with Membranes: Adding Back the Bilayer via High-Throughput Molecular Dynamics |
title | Interactions of Pleckstrin Homology Domains with Membranes: Adding Back the Bilayer via High-Throughput Molecular Dynamics |
title_full | Interactions of Pleckstrin Homology Domains with Membranes: Adding Back the Bilayer via High-Throughput Molecular Dynamics |
title_fullStr | Interactions of Pleckstrin Homology Domains with Membranes: Adding Back the Bilayer via High-Throughput Molecular Dynamics |
title_full_unstemmed | Interactions of Pleckstrin Homology Domains with Membranes: Adding Back the Bilayer via High-Throughput Molecular Dynamics |
title_short | Interactions of Pleckstrin Homology Domains with Membranes: Adding Back the Bilayer via High-Throughput Molecular Dynamics |
title_sort | interactions of pleckstrin homology domains with membranes: adding back the bilayer via high-throughput molecular dynamics |
topic | Theory |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975593/ https://www.ncbi.nlm.nih.gov/pubmed/27427480 http://dx.doi.org/10.1016/j.str.2016.06.002 |
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