Salt Bridge Formation between the I-BAR Domain and Lipids Increases Lipid Density and Membrane Curvature

Abstract The BAR domain superfamily proteins sense or induce curvature in membranes. The inverse-BAR domain (I-BAR) is a BAR domain that forms a straight “zeppelin-shaped” dimer. The mechanisms by which IRSp53 I-BAR binds to and deforms a lipid membrane are investigated here by all-atom molecular dy...

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Autores principales:	Kazuhiro Takemura, Kyoko Hanawa-Suetsugu, Shiro Suetsugu, Akio Kitao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2e4bc1121b3e447b80858d5efd481efc
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spelling	oai:doaj.org-article:2e4bc1121b3e447b80858d5efd481efc2021-12-02T12:32:32ZSalt Bridge Formation between the I-BAR Domain and Lipids Increases Lipid Density and Membrane Curvature10.1038/s41598-017-06334-52045-2322https://doaj.org/article/2e4bc1121b3e447b80858d5efd481efc2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06334-5https://doaj.org/toc/2045-2322Abstract The BAR domain superfamily proteins sense or induce curvature in membranes. The inverse-BAR domain (I-BAR) is a BAR domain that forms a straight “zeppelin-shaped” dimer. The mechanisms by which IRSp53 I-BAR binds to and deforms a lipid membrane are investigated here by all-atom molecular dynamics simulation (MD), binding energy analysis, and the effects of mutation experiments on filopodia on HeLa cells. I-BAR adopts a curved structure when crystallized, but adopts a flatter shape in MD. The binding of I-BAR to membrane was stabilized by ~30 salt bridges, consistent with experiments showing that point mutations of the interface residues have little effect on the binding affinity whereas multiple mutations have considerable effect. Salt bridge formation increases the local density of lipids and deforms the membrane into a concave shape. In addition, the point mutations that break key intra-molecular salt bridges within I-BAR reduce the binding affinity; this was confirmed by expressing these mutants in HeLa cells and observing their effects. The results indicate that the stiffness of I-BAR is important for membrane deformation, although I-BAR does not act as a completely rigid template.Kazuhiro TakemuraKyoko Hanawa-SuetsuguShiro SuetsuguAkio KitaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kazuhiro Takemura Kyoko Hanawa-Suetsugu Shiro Suetsugu Akio Kitao Salt Bridge Formation between the I-BAR Domain and Lipids Increases Lipid Density and Membrane Curvature
description	Abstract The BAR domain superfamily proteins sense or induce curvature in membranes. The inverse-BAR domain (I-BAR) is a BAR domain that forms a straight “zeppelin-shaped” dimer. The mechanisms by which IRSp53 I-BAR binds to and deforms a lipid membrane are investigated here by all-atom molecular dynamics simulation (MD), binding energy analysis, and the effects of mutation experiments on filopodia on HeLa cells. I-BAR adopts a curved structure when crystallized, but adopts a flatter shape in MD. The binding of I-BAR to membrane was stabilized by ~30 salt bridges, consistent with experiments showing that point mutations of the interface residues have little effect on the binding affinity whereas multiple mutations have considerable effect. Salt bridge formation increases the local density of lipids and deforms the membrane into a concave shape. In addition, the point mutations that break key intra-molecular salt bridges within I-BAR reduce the binding affinity; this was confirmed by expressing these mutants in HeLa cells and observing their effects. The results indicate that the stiffness of I-BAR is important for membrane deformation, although I-BAR does not act as a completely rigid template.
format	article
author	Kazuhiro Takemura Kyoko Hanawa-Suetsugu Shiro Suetsugu Akio Kitao
author_facet	Kazuhiro Takemura Kyoko Hanawa-Suetsugu Shiro Suetsugu Akio Kitao
author_sort	Kazuhiro Takemura
title	Salt Bridge Formation between the I-BAR Domain and Lipids Increases Lipid Density and Membrane Curvature
title_short	Salt Bridge Formation between the I-BAR Domain and Lipids Increases Lipid Density and Membrane Curvature
title_full	Salt Bridge Formation between the I-BAR Domain and Lipids Increases Lipid Density and Membrane Curvature
title_fullStr	Salt Bridge Formation between the I-BAR Domain and Lipids Increases Lipid Density and Membrane Curvature
title_full_unstemmed	Salt Bridge Formation between the I-BAR Domain and Lipids Increases Lipid Density and Membrane Curvature
title_sort	salt bridge formation between the i-bar domain and lipids increases lipid density and membrane curvature
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2e4bc1121b3e447b80858d5efd481efc
work_keys_str_mv	AT kazuhirotakemura saltbridgeformationbetweentheibardomainandlipidsincreaseslipiddensityandmembranecurvature AT kyokohanawasuetsugu saltbridgeformationbetweentheibardomainandlipidsincreaseslipiddensityandmembranecurvature AT shirosuetsugu saltbridgeformationbetweentheibardomainandlipidsincreaseslipiddensityandmembranecurvature AT akiokitao saltbridgeformationbetweentheibardomainandlipidsincreaseslipiddensityandmembranecurvature
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Salt Bridge Formation between the I-BAR Domain and Lipids Increases Lipid Density and Membrane Curvature

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