Forces and energetics of the canonical tetrameric cation channel gating.
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| Title: | Forces and energetics of the canonical tetrameric cation channel gating. |
|---|---|
| Authors: | Scheuring, Simon1,2,3 sis2019@med.cornell.edu |
| Source: | Proceedings of the National Academy of Sciences of the United States of America. 7/11/2023, Vol. 120 Issue 28, p1-9. 9p. |
| Subjects: | Potential energy, Force & energy, Cations, Single molecules, Ion channels |
| Abstract: | The canonical gating mechanism of tetrameric cation channels involves the spreading of the pore-lining helices at the so-called bundle-crossing gate. Despite a wealth of structural information, we lack a physical description of the gating process. Here, I took advantage of an entropic polymer stretching physical model and MthK structures to derive the forces and energies involved in pore-domain gating. In MthK, the Ca2+-induced conformational change in the RCK domain alone opens the bundle-crossing gate through pulling via unfolded linkers. In the open conformation, the linkers serve as entropic springs between the RCK domain and bundle-crossing gate that store an elastic potential energy of 3.6kBT and exert 9.8 pN (piconewton) radial pulling force to keep the gate open. I further derive that the work to load the linkers to prime the channel for opening is up to 3.8kBT, exerting up to 15.5 pN to pull the bundle-crossing open. Opening of the bundle-crossing leads to a release of 3.3kBT spring potential energy. Thus, the closed/RCK-apo and the open/RCK-Ca2+ conformations are separated by a barrier of several kBT. I discuss how these findings relate to the functional properties of MthK and suggest that given the architectural conservation of the helix–pore-loop–helix pore-domain among all tetrameric cation channels, these physical parameters might be quite general. [ABSTRACT FROM AUTHOR] |
| Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 168777363 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Forces and energetics of the canonical tetrameric cation channel gating. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Scheuring%2C+Simon%22">Scheuring, Simon</searchLink><relatesTo>1,2,3</relatesTo><i> sis2019@med.cornell.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America%22">Proceedings of the National Academy of Sciences of the United States of America</searchLink>. 7/11/2023, Vol. 120 Issue 28, p1-9. 9p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Potential+energy%22">Potential energy</searchLink><br /><searchLink fieldCode="DE" term="%22Force+%26+energy%22">Force & energy</searchLink><br /><searchLink fieldCode="DE" term="%22Cations%22">Cations</searchLink><br /><searchLink fieldCode="DE" term="%22Single+molecules%22">Single molecules</searchLink><br /><searchLink fieldCode="DE" term="%22Ion+channels%22">Ion channels</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: The canonical gating mechanism of tetrameric cation channels involves the spreading of the pore-lining helices at the so-called bundle-crossing gate. Despite a wealth of structural information, we lack a physical description of the gating process. Here, I took advantage of an entropic polymer stretching physical model and MthK structures to derive the forces and energies involved in pore-domain gating. In MthK, the Ca2+-induced conformational change in the RCK domain alone opens the bundle-crossing gate through pulling via unfolded linkers. In the open conformation, the linkers serve as entropic springs between the RCK domain and bundle-crossing gate that store an elastic potential energy of 3.6kBT and exert 9.8 pN (piconewton) radial pulling force to keep the gate open. I further derive that the work to load the linkers to prime the channel for opening is up to 3.8kBT, exerting up to 15.5 pN to pull the bundle-crossing open. Opening of the bundle-crossing leads to a release of 3.3kBT spring potential energy. Thus, the closed/RCK-apo and the open/RCK-Ca2+ conformations are separated by a barrier of several kBT. I discuss how these findings relate to the functional properties of MthK and suggest that given the architectural conservation of the helix–pore-loop–helix pore-domain among all tetrameric cation channels, these physical parameters might be quite general. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1073/pnas.2221616120 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 9 StartPage: 1 Subjects: – SubjectFull: Potential energy Type: general – SubjectFull: Force & energy Type: general – SubjectFull: Cations Type: general – SubjectFull: Single molecules Type: general – SubjectFull: Ion channels Type: general Titles: – TitleFull: Forces and energetics of the canonical tetrameric cation channel gating. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Scheuring, Simon IsPartOfRelationships: – BibEntity: Dates: – D: 11 M: 07 Text: 7/11/2023 Type: published Y: 2023 Identifiers: – Type: issn-print Value: 00278424 Numbering: – Type: volume Value: 120 – Type: issue Value: 28 Titles: – TitleFull: Proceedings of the National Academy of Sciences of the United States of America Type: main |
| ResultId | 1 |
