Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets
Lipid availability within transmembrane nano-pockets of ion channels is linked with mechanosensation. However, the effect of hindering lipid-chain penetration into nano-pockets on channel structure has not been demonstrated. Here we identify nano-pockets on the large conductance mechanosensitive cha...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2019
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| _version_ | 1797072255418630144 |
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| author | Kapsalis, C Wang, B El Mkami, H Pitt, SJ Schnell, JR Smith, TK Lippiat, JD Bode, BE Pliotas, C |
| author_facet | Kapsalis, C Wang, B El Mkami, H Pitt, SJ Schnell, JR Smith, TK Lippiat, JD Bode, BE Pliotas, C |
| author_sort | Kapsalis, C |
| collection | OXFORD |
| description | Lipid availability within transmembrane nano-pockets of ion channels is linked with mechanosensation. However, the effect of hindering lipid-chain penetration into nano-pockets on channel structure has not been demonstrated. Here we identify nano-pockets on the large conductance mechanosensitive channel MscL, the high-pressure threshold channel. We restrict lipid-chain access to the nano-pockets by mutagenesis and sulfhydryl modification, and monitor channel conformation by PELDOR/DEER spectroscopy. For a single site located at the entrance of the nano-pockets and distal to the channel pore we generate an allosteric response in the absence of tension. Single-channel recordings reveal a significant decrease in the pressure activation threshold of the modified channel and a sub-conducting state in the absence of applied tension. Threshold is restored to wild-type levels upon reduction of the sulfhydryl modification. The modification associated with the conformational change restricts lipid access to the nano-pocket, interrupting the contact between the membrane and the channel that mediates mechanosensitivity. |
| first_indexed | 2024-03-06T23:05:06Z |
| format | Journal article |
| id | oxford-uuid:6380eac0-01a7-4c0b-86a6-cfb0d3236d6a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:05:06Z |
| publishDate | 2019 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:6380eac0-01a7-4c0b-86a6-cfb0d3236d6a2022-03-26T18:13:31ZAllosteric activation of an ion channel triggered by modification of mechanosensitive nano-pocketsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6380eac0-01a7-4c0b-86a6-cfb0d3236d6aEnglishSymplectic ElementsSpringer Nature2019Kapsalis, CWang, BEl Mkami, HPitt, SJSchnell, JRSmith, TKLippiat, JDBode, BEPliotas, CLipid availability within transmembrane nano-pockets of ion channels is linked with mechanosensation. However, the effect of hindering lipid-chain penetration into nano-pockets on channel structure has not been demonstrated. Here we identify nano-pockets on the large conductance mechanosensitive channel MscL, the high-pressure threshold channel. We restrict lipid-chain access to the nano-pockets by mutagenesis and sulfhydryl modification, and monitor channel conformation by PELDOR/DEER spectroscopy. For a single site located at the entrance of the nano-pockets and distal to the channel pore we generate an allosteric response in the absence of tension. Single-channel recordings reveal a significant decrease in the pressure activation threshold of the modified channel and a sub-conducting state in the absence of applied tension. Threshold is restored to wild-type levels upon reduction of the sulfhydryl modification. The modification associated with the conformational change restricts lipid access to the nano-pocket, interrupting the contact between the membrane and the channel that mediates mechanosensitivity. |
| spellingShingle | Kapsalis, C Wang, B El Mkami, H Pitt, SJ Schnell, JR Smith, TK Lippiat, JD Bode, BE Pliotas, C Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets |
| title | Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets |
| title_full | Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets |
| title_fullStr | Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets |
| title_full_unstemmed | Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets |
| title_short | Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets |
| title_sort | allosteric activation of an ion channel triggered by modification of mechanosensitive nano pockets |
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