Structural Investigation of MscL Gating Using Experimental Data and Coarse Grained MD Simulations
The mechanosensitive channel of large conductance (MscL) has become a model system in which to understand mechanosensation, a process involved in osmoregulation and many other physiological functions. While a high resolution closed state structure is available, details of the open structure and the...
| Main Authors: | , , , , |
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| Format: | Journal Article |
| Published: |
2012
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| Online Access: | http://hdl.handle.net/20.500.11937/4858 |
| _version_ | 1848744634374684672 |
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| author | Deplazes, Evelyne Louhivuori, M. Jayatilaka, D. Marrink, S. Corry, B. |
| author_facet | Deplazes, Evelyne Louhivuori, M. Jayatilaka, D. Marrink, S. Corry, B. |
| author_sort | Deplazes, Evelyne |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | The mechanosensitive channel of large conductance (MscL) has become a model system in which to understand mechanosensation, a process involved in osmoregulation and many other physiological functions. While a high resolution closed state structure is available, details of the open structure and the gating mechanism remain unknown. In this study we combine coarse grained simulations with restraints from EPR and FRET experiments to study the structural changes involved in gating with much greater level of conformational sampling than has previously been possible. We generated a set of plausible open pore structures that agree well with existing open pore structures and gating models. Most interestingly, we found that membrane thinning induces a kink in the upper part of TM1 that causes an outward motion of the periplasmic loop away from the pore centre. This previously unobserved structural change might present a new mechanism of tension sensing and might be related to a functional role in osmoregulation. |
| first_indexed | 2025-11-14T06:04:35Z |
| format | Journal Article |
| id | curtin-20.500.11937-4858 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:04:35Z |
| publishDate | 2012 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-48582017-09-13T14:45:10Z Structural Investigation of MscL Gating Using Experimental Data and Coarse Grained MD Simulations Deplazes, Evelyne Louhivuori, M. Jayatilaka, D. Marrink, S. Corry, B. The mechanosensitive channel of large conductance (MscL) has become a model system in which to understand mechanosensation, a process involved in osmoregulation and many other physiological functions. While a high resolution closed state structure is available, details of the open structure and the gating mechanism remain unknown. In this study we combine coarse grained simulations with restraints from EPR and FRET experiments to study the structural changes involved in gating with much greater level of conformational sampling than has previously been possible. We generated a set of plausible open pore structures that agree well with existing open pore structures and gating models. Most interestingly, we found that membrane thinning induces a kink in the upper part of TM1 that causes an outward motion of the periplasmic loop away from the pore centre. This previously unobserved structural change might present a new mechanism of tension sensing and might be related to a functional role in osmoregulation. 2012 Journal Article http://hdl.handle.net/20.500.11937/4858 10.1371/journal.pcbi.1002683 fulltext |
| spellingShingle | Deplazes, Evelyne Louhivuori, M. Jayatilaka, D. Marrink, S. Corry, B. Structural Investigation of MscL Gating Using Experimental Data and Coarse Grained MD Simulations |
| title | Structural Investigation of MscL Gating Using Experimental Data and Coarse Grained MD Simulations |
| title_full | Structural Investigation of MscL Gating Using Experimental Data and Coarse Grained MD Simulations |
| title_fullStr | Structural Investigation of MscL Gating Using Experimental Data and Coarse Grained MD Simulations |
| title_full_unstemmed | Structural Investigation of MscL Gating Using Experimental Data and Coarse Grained MD Simulations |
| title_short | Structural Investigation of MscL Gating Using Experimental Data and Coarse Grained MD Simulations |
| title_sort | structural investigation of mscl gating using experimental data and coarse grained md simulations |
| url | http://hdl.handle.net/20.500.11937/4858 |