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Hydrophobic Coupling of Lipid Bilayer Energetics to Channel Function
The hydrophobic coupling between membrane-spanning proteins and the lipid bilayer core causes the bilayer thickness to vary locally as proteins and other “defects” are embedded in the bilayer. These bilayer deformations incur an energetic cost that, in principle, could couple membrane proteins to ea...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2217378/ https://www.ncbi.nlm.nih.gov/pubmed/12719487 http://dx.doi.org/10.1085/jgp.200308797 |
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author | Goforth, Robyn L. Chi, Aung K. Greathouse, Denise V. Providence, Lyndon L. Koeppe, Roger E. Andersen, Olaf S. |
author_facet | Goforth, Robyn L. Chi, Aung K. Greathouse, Denise V. Providence, Lyndon L. Koeppe, Roger E. Andersen, Olaf S. |
author_sort | Goforth, Robyn L. |
collection | PubMed |
description | The hydrophobic coupling between membrane-spanning proteins and the lipid bilayer core causes the bilayer thickness to vary locally as proteins and other “defects” are embedded in the bilayer. These bilayer deformations incur an energetic cost that, in principle, could couple membrane proteins to each other, causing them to associate in the plane of the membrane and thereby coupling them functionally. We demonstrate the existence of such bilayer-mediated coupling at the single-molecule level using single-barreled as well as double-barreled gramicidin channels in which two gramicidin subunits are covalently linked by a water-soluble, flexible linker. When a covalently attached pair of gramicidin subunits associates with a second attached pair to form a double-barreled channel, the lifetime of both channels in the assembly increases from hundreds of milliseconds to a hundred seconds—and the conductance of each channel in the side-by-side pair is almost 10% higher than the conductance of the corresponding single-barreled channels. The double-barreled channels are stabilized some 100,000-fold relative to their single-barreled counterparts. This stabilization arises from: first, the local increase in monomer concentration around a single-barreled channel formed by two covalently linked gramicidins, which increases the rate of double-barreled channel formation; and second, from the increased lifetime of the double-barreled channels. The latter result suggests that the two barrels of the construct associate laterally. The underlying cause for this lateral association most likely is the bilayer deformation energy associated with channel formation. More generally, the results suggest that the mechanical properties of the host bilayer may cause the kinetics of membrane protein conformational transitions to depend on the conformational states of the neighboring proteins. |
format | Text |
id | pubmed-2217378 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22173782008-04-16 Hydrophobic Coupling of Lipid Bilayer Energetics to Channel Function Goforth, Robyn L. Chi, Aung K. Greathouse, Denise V. Providence, Lyndon L. Koeppe, Roger E. Andersen, Olaf S. J Gen Physiol Article The hydrophobic coupling between membrane-spanning proteins and the lipid bilayer core causes the bilayer thickness to vary locally as proteins and other “defects” are embedded in the bilayer. These bilayer deformations incur an energetic cost that, in principle, could couple membrane proteins to each other, causing them to associate in the plane of the membrane and thereby coupling them functionally. We demonstrate the existence of such bilayer-mediated coupling at the single-molecule level using single-barreled as well as double-barreled gramicidin channels in which two gramicidin subunits are covalently linked by a water-soluble, flexible linker. When a covalently attached pair of gramicidin subunits associates with a second attached pair to form a double-barreled channel, the lifetime of both channels in the assembly increases from hundreds of milliseconds to a hundred seconds—and the conductance of each channel in the side-by-side pair is almost 10% higher than the conductance of the corresponding single-barreled channels. The double-barreled channels are stabilized some 100,000-fold relative to their single-barreled counterparts. This stabilization arises from: first, the local increase in monomer concentration around a single-barreled channel formed by two covalently linked gramicidins, which increases the rate of double-barreled channel formation; and second, from the increased lifetime of the double-barreled channels. The latter result suggests that the two barrels of the construct associate laterally. The underlying cause for this lateral association most likely is the bilayer deformation energy associated with channel formation. More generally, the results suggest that the mechanical properties of the host bilayer may cause the kinetics of membrane protein conformational transitions to depend on the conformational states of the neighboring proteins. The Rockefeller University Press 2003-05 /pmc/articles/PMC2217378/ /pubmed/12719487 http://dx.doi.org/10.1085/jgp.200308797 Text en Copyright © 2003, The Rockefeller University Press 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.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Goforth, Robyn L. Chi, Aung K. Greathouse, Denise V. Providence, Lyndon L. Koeppe, Roger E. Andersen, Olaf S. Hydrophobic Coupling of Lipid Bilayer Energetics to Channel Function |
title | Hydrophobic Coupling of Lipid Bilayer Energetics to Channel Function |
title_full | Hydrophobic Coupling of Lipid Bilayer Energetics to Channel Function |
title_fullStr | Hydrophobic Coupling of Lipid Bilayer Energetics to Channel Function |
title_full_unstemmed | Hydrophobic Coupling of Lipid Bilayer Energetics to Channel Function |
title_short | Hydrophobic Coupling of Lipid Bilayer Energetics to Channel Function |
title_sort | hydrophobic coupling of lipid bilayer energetics to channel function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2217378/ https://www.ncbi.nlm.nih.gov/pubmed/12719487 http://dx.doi.org/10.1085/jgp.200308797 |
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