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Force Transduction and Lipid Binding in MscL: A Continuum-Molecular Approach
The bacterial mechanosensitive channel MscL, a small protein mainly activated by membrane tension, is a central model system to study the transduction of mechanical stimuli into chemical signals. Mutagenic studies suggest that MscL gating strongly depends on both intra-protein and interfacial lipid-...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250078/ https://www.ncbi.nlm.nih.gov/pubmed/25437007 http://dx.doi.org/10.1371/journal.pone.0113947 |
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author | Vanegas, Juan M. Arroyo, Marino |
author_facet | Vanegas, Juan M. Arroyo, Marino |
author_sort | Vanegas, Juan M. |
collection | PubMed |
description | The bacterial mechanosensitive channel MscL, a small protein mainly activated by membrane tension, is a central model system to study the transduction of mechanical stimuli into chemical signals. Mutagenic studies suggest that MscL gating strongly depends on both intra-protein and interfacial lipid-protein interactions. However, there is a gap between this detailed chemical information and current mechanical models of MscL gating. Here, we investigate the MscL bilayer-protein interface through molecular dynamics simulations, and take a combined continuum-molecular approach to connect chemistry and mechanics. We quantify the effect of membrane tension on the forces acting on the surface of the channel, and identify interactions that may be critical in the force transduction between the membrane and MscL. We find that the local stress distribution on the protein surface is largely asymmetric, particularly under tension, with the cytoplasmic side showing significantly larger and more localized forces, which pull the protein radially outward. The molecular interactions that mediate this behavior arise from hydrogen bonds between the electronegative oxygens in the lipid headgroup and a cluster of positively charged lysine residues on the amphipathic S1 domain and the C-terminal end of the second trans-membrane helix. We take advantage of this strong interaction (estimated to be 10–13 kT per lipid) to actuate the channel (by applying forces on protein-bound lipids) and explore its sensitivity to the pulling magnitude and direction. We conclude by highlighting the simple motif that confers MscL with strong anchoring to the bilayer, and its presence in various integral membrane proteins including the human mechanosensitive channel K2P1 and bovine rhodopsin. |
format | Online Article Text |
id | pubmed-4250078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42500782014-12-05 Force Transduction and Lipid Binding in MscL: A Continuum-Molecular Approach Vanegas, Juan M. Arroyo, Marino PLoS One Research Article The bacterial mechanosensitive channel MscL, a small protein mainly activated by membrane tension, is a central model system to study the transduction of mechanical stimuli into chemical signals. Mutagenic studies suggest that MscL gating strongly depends on both intra-protein and interfacial lipid-protein interactions. However, there is a gap between this detailed chemical information and current mechanical models of MscL gating. Here, we investigate the MscL bilayer-protein interface through molecular dynamics simulations, and take a combined continuum-molecular approach to connect chemistry and mechanics. We quantify the effect of membrane tension on the forces acting on the surface of the channel, and identify interactions that may be critical in the force transduction between the membrane and MscL. We find that the local stress distribution on the protein surface is largely asymmetric, particularly under tension, with the cytoplasmic side showing significantly larger and more localized forces, which pull the protein radially outward. The molecular interactions that mediate this behavior arise from hydrogen bonds between the electronegative oxygens in the lipid headgroup and a cluster of positively charged lysine residues on the amphipathic S1 domain and the C-terminal end of the second trans-membrane helix. We take advantage of this strong interaction (estimated to be 10–13 kT per lipid) to actuate the channel (by applying forces on protein-bound lipids) and explore its sensitivity to the pulling magnitude and direction. We conclude by highlighting the simple motif that confers MscL with strong anchoring to the bilayer, and its presence in various integral membrane proteins including the human mechanosensitive channel K2P1 and bovine rhodopsin. Public Library of Science 2014-12-01 /pmc/articles/PMC4250078/ /pubmed/25437007 http://dx.doi.org/10.1371/journal.pone.0113947 Text en © 2014 Vanegas, Arroyo http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Vanegas, Juan M. Arroyo, Marino Force Transduction and Lipid Binding in MscL: A Continuum-Molecular Approach |
title | Force Transduction and Lipid Binding in MscL: A Continuum-Molecular Approach |
title_full | Force Transduction and Lipid Binding in MscL: A Continuum-Molecular Approach |
title_fullStr | Force Transduction and Lipid Binding in MscL: A Continuum-Molecular Approach |
title_full_unstemmed | Force Transduction and Lipid Binding in MscL: A Continuum-Molecular Approach |
title_short | Force Transduction and Lipid Binding in MscL: A Continuum-Molecular Approach |
title_sort | force transduction and lipid binding in mscl: a continuum-molecular approach |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250078/ https://www.ncbi.nlm.nih.gov/pubmed/25437007 http://dx.doi.org/10.1371/journal.pone.0113947 |
work_keys_str_mv | AT vanegasjuanm forcetransductionandlipidbindinginmsclacontinuummolecularapproach AT arroyomarino forcetransductionandlipidbindinginmsclacontinuummolecularapproach |