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To flip or not to flip: lipid–protein charge interactions are a determinant of final membrane protein topology

The molecular details of how lipids influence final topological organization of membrane proteins are not well understood. Here, we present evidence that final topology is influenced by lipid–protein interactions most likely outside of the translocon. The N-terminal half of Escherichia coli lactose...

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Detalles Bibliográficos
Autores principales: Bogdanov, Mikhail, Xie, Jun, Heacock, Phil, Dowhan, William
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528571/
https://www.ncbi.nlm.nih.gov/pubmed/18779371
http://dx.doi.org/10.1083/jcb.200803097
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author Bogdanov, Mikhail
Xie, Jun
Heacock, Phil
Dowhan, William
author_facet Bogdanov, Mikhail
Xie, Jun
Heacock, Phil
Dowhan, William
author_sort Bogdanov, Mikhail
collection PubMed
description The molecular details of how lipids influence final topological organization of membrane proteins are not well understood. Here, we present evidence that final topology is influenced by lipid–protein interactions most likely outside of the translocon. The N-terminal half of Escherichia coli lactose permease (LacY) is inverted with respect to the C-terminal half and the membrane bilayer when assembled in mutants lacking phosphatidylethanolamine and containing only negatively charged phospholipids. We demonstrate that inversion is dependent on interactions between the net charge of the cytoplasmic surface of the N-terminal bundle and the negative charge density of the membrane bilayer surface. A transmembrane domain, acting as a molecular hinge between the two halves of the protein, must also exit from the membrane for inversion to occur. Phosphatidylethanolamine dampens the translocation potential of negative residues in favor of the cytoplasmic retention potential of positive residues, thus explaining the dominance of positive over negative amino acids as co- or post-translational topological determinants.
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spelling pubmed-25285712009-03-08 To flip or not to flip: lipid–protein charge interactions are a determinant of final membrane protein topology Bogdanov, Mikhail Xie, Jun Heacock, Phil Dowhan, William J Cell Biol Research Articles The molecular details of how lipids influence final topological organization of membrane proteins are not well understood. Here, we present evidence that final topology is influenced by lipid–protein interactions most likely outside of the translocon. The N-terminal half of Escherichia coli lactose permease (LacY) is inverted with respect to the C-terminal half and the membrane bilayer when assembled in mutants lacking phosphatidylethanolamine and containing only negatively charged phospholipids. We demonstrate that inversion is dependent on interactions between the net charge of the cytoplasmic surface of the N-terminal bundle and the negative charge density of the membrane bilayer surface. A transmembrane domain, acting as a molecular hinge between the two halves of the protein, must also exit from the membrane for inversion to occur. Phosphatidylethanolamine dampens the translocation potential of negative residues in favor of the cytoplasmic retention potential of positive residues, thus explaining the dominance of positive over negative amino acids as co- or post-translational topological determinants. The Rockefeller University Press 2008-09-08 /pmc/articles/PMC2528571/ /pubmed/18779371 http://dx.doi.org/10.1083/jcb.200803097 Text en © 2008 Bogdanov et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Bogdanov, Mikhail
Xie, Jun
Heacock, Phil
Dowhan, William
To flip or not to flip: lipid–protein charge interactions are a determinant of final membrane protein topology
title To flip or not to flip: lipid–protein charge interactions are a determinant of final membrane protein topology
title_full To flip or not to flip: lipid–protein charge interactions are a determinant of final membrane protein topology
title_fullStr To flip or not to flip: lipid–protein charge interactions are a determinant of final membrane protein topology
title_full_unstemmed To flip or not to flip: lipid–protein charge interactions are a determinant of final membrane protein topology
title_short To flip or not to flip: lipid–protein charge interactions are a determinant of final membrane protein topology
title_sort to flip or not to flip: lipid–protein charge interactions are a determinant of final membrane protein topology
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528571/
https://www.ncbi.nlm.nih.gov/pubmed/18779371
http://dx.doi.org/10.1083/jcb.200803097
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