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Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes

Association of peripheral proteins with lipid bilayers regulates membrane signaling and dynamics. Pleckstrin homology (PH) domains bind to phosphatidylinositol phosphate (PIP) molecules in membranes. The effects of local PIP enrichment on the interaction of PH domains with membranes is unclear. Mole...

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Autores principales: Yamamoto, Eiji, Domański, Jan, Naughton, Fiona B., Best, Robert B., Kalli, Antreas C., Stansfeld, Phillip J., Sansom, Mark S. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030919/
https://www.ncbi.nlm.nih.gov/pubmed/32128410
http://dx.doi.org/10.1126/sciadv.aay5736
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author Yamamoto, Eiji
Domański, Jan
Naughton, Fiona B.
Best, Robert B.
Kalli, Antreas C.
Stansfeld, Phillip J.
Sansom, Mark S. P.
author_facet Yamamoto, Eiji
Domański, Jan
Naughton, Fiona B.
Best, Robert B.
Kalli, Antreas C.
Stansfeld, Phillip J.
Sansom, Mark S. P.
author_sort Yamamoto, Eiji
collection PubMed
description Association of peripheral proteins with lipid bilayers regulates membrane signaling and dynamics. Pleckstrin homology (PH) domains bind to phosphatidylinositol phosphate (PIP) molecules in membranes. The effects of local PIP enrichment on the interaction of PH domains with membranes is unclear. Molecular dynamics simulations allow estimation of the binding energy of GRP1 PH domain to PIP(3)-containing membranes. The free energy of interaction of the PH domain with more than two PIP(3) molecules is comparable to experimental values, suggesting that PH domain binding involves local clustering of PIP molecules within membranes. We describe a mechanism of PH binding proceeding via an encounter state to two bound states which differ in the orientation of the protein relative to the membrane, these orientations depending on the local PIP concentration. These results suggest that nanoscale clustering of PIP molecules can control the strength and orientation of PH domain interaction in a concentration-dependent manner.
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spelling pubmed-70309192020-03-03 Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes Yamamoto, Eiji Domański, Jan Naughton, Fiona B. Best, Robert B. Kalli, Antreas C. Stansfeld, Phillip J. Sansom, Mark S. P. Sci Adv Research Articles Association of peripheral proteins with lipid bilayers regulates membrane signaling and dynamics. Pleckstrin homology (PH) domains bind to phosphatidylinositol phosphate (PIP) molecules in membranes. The effects of local PIP enrichment on the interaction of PH domains with membranes is unclear. Molecular dynamics simulations allow estimation of the binding energy of GRP1 PH domain to PIP(3)-containing membranes. The free energy of interaction of the PH domain with more than two PIP(3) molecules is comparable to experimental values, suggesting that PH domain binding involves local clustering of PIP molecules within membranes. We describe a mechanism of PH binding proceeding via an encounter state to two bound states which differ in the orientation of the protein relative to the membrane, these orientations depending on the local PIP concentration. These results suggest that nanoscale clustering of PIP molecules can control the strength and orientation of PH domain interaction in a concentration-dependent manner. American Association for the Advancement of Science 2020-02-19 /pmc/articles/PMC7030919/ /pubmed/32128410 http://dx.doi.org/10.1126/sciadv.aay5736 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). 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 work is properly cited.
spellingShingle Research Articles
Yamamoto, Eiji
Domański, Jan
Naughton, Fiona B.
Best, Robert B.
Kalli, Antreas C.
Stansfeld, Phillip J.
Sansom, Mark S. P.
Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes
title Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes
title_full Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes
title_fullStr Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes
title_full_unstemmed Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes
title_short Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes
title_sort multiple lipid binding sites determine the affinity of ph domains for phosphoinositide-containing membranes
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030919/
https://www.ncbi.nlm.nih.gov/pubmed/32128410
http://dx.doi.org/10.1126/sciadv.aay5736
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