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: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC3447979?pdf=render |
| _version_ | 1830411077523865600 |
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| author | Evelyne Deplazes Martti Louhivuori Dylan Jayatilaka Siewert J Marrink Ben Corry |
| author_facet | Evelyne Deplazes Martti Louhivuori Dylan Jayatilaka Siewert J Marrink Ben Corry |
| author_sort | Evelyne Deplazes |
| collection | DOAJ |
| 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 | 2024-12-20T19:43:18Z |
| format | Article |
| id | doaj.art-25093cc7f5f74b4e83c65beab09f692b |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-20T19:43:18Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-25093cc7f5f74b4e83c65beab09f692b2022-12-21T19:28:29ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582012-01-0189e100268310.1371/journal.pcbi.1002683Structural investigation of MscL gating using experimental data and coarse grained MD simulations.Evelyne DeplazesMartti LouhivuoriDylan JayatilakaSiewert J MarrinkBen CorryThe 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.http://europepmc.org/articles/PMC3447979?pdf=render |
| spellingShingle | Evelyne Deplazes Martti Louhivuori Dylan Jayatilaka Siewert J Marrink Ben Corry Structural investigation of MscL gating using experimental data and coarse grained MD simulations. PLoS Computational Biology |
| 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://europepmc.org/articles/PMC3447979?pdf=render |
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