Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS
Prokaryotic mechanosensitive (MS) channels open by sensing the physical state of the membrane. As such, lipid-protein interactions represent the defining molecular process underlying mechanotransduction. Here, we describe cryo-electron microscopy (cryo-EM) structures of the E. coli small-conductance...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2019-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/50486 |
| _version_ | 1818023819967725568 |
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| author | Bharat Reddy Navid Bavi Allen Lu Yeonwoo Park Eduardo Perozo |
| author_facet | Bharat Reddy Navid Bavi Allen Lu Yeonwoo Park Eduardo Perozo |
| author_sort | Bharat Reddy |
| collection | DOAJ |
| description | Prokaryotic mechanosensitive (MS) channels open by sensing the physical state of the membrane. As such, lipid-protein interactions represent the defining molecular process underlying mechanotransduction. Here, we describe cryo-electron microscopy (cryo-EM) structures of the E. coli small-conductance mechanosensitive channel (MscS) in nanodiscs (ND). They reveal a novel membrane-anchoring fold that plays a significant role in channel activation and establish a new location for the lipid bilayer, shifted ~14 Å from previous consensus placements. Two types of lipid densities are explicitly observed. A phospholipid that ‘hooks’ the top of each TM2-TM3 hairpin and likely plays a role in force sensing, and a bundle of acyl chains occluding the permeation path above the L105 cuff. These observations reshape our understanding of force-from-lipids gating in MscS and highlight the key role of allosteric interactions between TM segments and phospholipids bound to key dynamic components of the channel. |
| first_indexed | 2024-12-10T03:50:23Z |
| format | Article |
| id | doaj.art-9a4e7fb91ebf45fdaac1e110c653e491 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T03:50:23Z |
| publishDate | 2019-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-9a4e7fb91ebf45fdaac1e110c653e4912022-12-22T02:03:16ZengeLife Sciences Publications LtdeLife2050-084X2019-12-01810.7554/eLife.50486Molecular basis of force-from-lipids gating in the mechanosensitive channel MscSBharat Reddy0Navid Bavi1Allen Lu2Yeonwoo Park3Eduardo Perozo4https://orcid.org/0000-0001-7132-2793Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United StatesDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United StatesDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United StatesDepartment of Ecology and Evolution, The University of Chicago, Chicago, United StatesDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States; Institute for Biophysical Dynamics, The University of Chicago, Chicago, United StatesProkaryotic mechanosensitive (MS) channels open by sensing the physical state of the membrane. As such, lipid-protein interactions represent the defining molecular process underlying mechanotransduction. Here, we describe cryo-electron microscopy (cryo-EM) structures of the E. coli small-conductance mechanosensitive channel (MscS) in nanodiscs (ND). They reveal a novel membrane-anchoring fold that plays a significant role in channel activation and establish a new location for the lipid bilayer, shifted ~14 Å from previous consensus placements. Two types of lipid densities are explicitly observed. A phospholipid that ‘hooks’ the top of each TM2-TM3 hairpin and likely plays a role in force sensing, and a bundle of acyl chains occluding the permeation path above the L105 cuff. These observations reshape our understanding of force-from-lipids gating in MscS and highlight the key role of allosteric interactions between TM segments and phospholipids bound to key dynamic components of the channel.https://elifesciences.org/articles/50486mechanotransductionforce-from-lipid gatingMscSCryo-EM |
| spellingShingle | Bharat Reddy Navid Bavi Allen Lu Yeonwoo Park Eduardo Perozo Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS eLife mechanotransduction force-from-lipid gating MscS Cryo-EM |
| title | Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS |
| title_full | Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS |
| title_fullStr | Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS |
| title_full_unstemmed | Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS |
| title_short | Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS |
| title_sort | molecular basis of force from lipids gating in the mechanosensitive channel mscs |
| topic | mechanotransduction force-from-lipid gating MscS Cryo-EM |
| url | https://elifesciences.org/articles/50486 |
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