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dc.contributor.authorKapsalis, Charalampos
dc.contributor.authorWang, Bolin
dc.contributor.authorEl Mkami, Hassane
dc.contributor.authorPitt, Samantha Jane
dc.contributor.authorSchnell, Jason
dc.contributor.authorSmith, Terry K.
dc.contributor.authorLippiat, Jonathan
dc.contributor.authorBode, Bela E.
dc.contributor.authorPliotas, Christos
dc.date.accessioned2019-10-11T08:30:07Z
dc.date.available2019-10-11T08:30:07Z
dc.date.issued2019-10-10
dc.identifier.citationKapsalis , C , Wang , B , El Mkami , H , Pitt , S J , Schnell , J , Smith , T K , Lippiat , J , Bode , B E & Pliotas , C 2019 , ' Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets ' , Nature Communications , vol. 10 , 4619 . https://doi.org/10.1038/s41467-019-12591-xen
dc.identifier.issn2041-1723
dc.identifier.otherPURE: 261215719
dc.identifier.otherPURE UUID: 5cc05632-0041-4fa5-9b84-7e02af6644f1
dc.identifier.otherORCID: /0000-0002-0552-5784/work/63044335
dc.identifier.otherORCID: /0000-0002-4309-4858/work/63045600
dc.identifier.otherORCID: /0000-0002-3384-271X/work/63045818
dc.identifier.otherORCID: /0000-0003-2257-1595/work/63045826
dc.identifier.otherScopus: 85073115666
dc.identifier.otherWOS: 000489558100002
dc.identifier.urihttp://hdl.handle.net/10023/18643
dc.descriptionC.P. is supported by the Royal Society of Edinburgh. C.P. acknowledges support by Tenovus (T15/41) and Carnegie Trust (OS000256) and the University of St Andrews, the University of Leeds and the Chinese Scholarship Council for the C.K. and B.W. studentships respectively. S.J.P. is supported by the Royal Society of Edinburgh. J.S. acknowledges funding from the MRC (M019152 and L018578). B.E.B. and C.P. acknowledge support by the Leverhulme Trust (RPG-2018-397). This work was supported by Wellcome Trust [099149/Z/12/Z] and BBSRC equipment grants (BB/R013780/1).en
dc.description.abstractLipid 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. 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 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, and interrupts the contact between the membrane and the channel that mediates mechanosensitivity.
dc.format.extent14
dc.language.isoeng
dc.relation.ispartofNature Communicationsen
dc.rightsCopyright © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en
dc.subjectQD Chemistryen
dc.subjectQH301 Biologyen
dc.subjectDASen
dc.subjectBDCen
dc.subjectR2Cen
dc.subject.lccQDen
dc.subject.lccQH301en
dc.titleAllosteric activation of an ion channel triggered by modification of mechanosensitive nano-pocketsen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.School of Physics and Astronomyen
dc.contributor.institutionUniversity of St Andrews.Centre for Biophotonicsen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews.Centre of Magnetic Resonanceen
dc.contributor.institutionUniversity of St Andrews.School of Chemistryen
dc.identifier.doihttps://doi.org/10.1038/s41467-019-12591-x
dc.description.statusPeer revieweden
dc.date.embargoedUntil2019-10-10


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