Cyclodextrins for structural and functional studies of mechanosensitive channels

Mechanosensitive (MS) channels that are activated by the ‘force-from-lipids’ (FFL) principle rest in the membrane in a closed state but open a transmembrane pore in response to changes in the transmembrane pressure profile. The molecular implementations of the FFL principle vary widely between diffe...

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Autores principales: Yixiao Zhang, Gabriella Angiulli, Boris Martinac, Charles D. Cox, Thomas Walz
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Lenguaje:EN
Publicado: Elsevier 2021
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spelling oai:doaj.org-article:47ab7ce7f62e47e98fe15b59081ccb282021-11-14T04:35:23ZCyclodextrins for structural and functional studies of mechanosensitive channels2590-152410.1016/j.yjsbx.2021.100053https://doaj.org/article/47ab7ce7f62e47e98fe15b59081ccb282021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2590152421000106https://doaj.org/toc/2590-1524Mechanosensitive (MS) channels that are activated by the ‘force-from-lipids’ (FFL) principle rest in the membrane in a closed state but open a transmembrane pore in response to changes in the transmembrane pressure profile. The molecular implementations of the FFL principle vary widely between different MS channel families. The function of MS channels is often studied by patch-clamp electrophysiology, in which mechanical force or amphipathic molecules are used to activate the channels. Structural studies of MS channels in states other than the closed resting state typically relied on the use of mutant channels. Cyclodextrins (CDs) were recently introduced as a relatively easy and convenient approach to generate membrane tension. The principle is that CDs chelate hydrophobic molecules and can remove lipids from membranes, thus forcing the remaining lipids to cover more surface area and creating tension for membrane proteins residing in the membranes. CDs can be used to study the structure of MS channels in a membrane under tension by using single-particle cryo-electron microscopy to image the channels in nanodiscs after incubation with CDs as well as to characterize the function of MS channels by using patch-clamp electrophysiology to record the effect of CDs on channels inserted into membrane patches excised from proteoliposomes. Importantly, because incubation of membrane patches with CDs results in the activation of MscL, an MS channel that opens only shortly before membrane rupture, CD-mediated lipid removal appears to generate sufficient force to open most if not all types of MS channels that follow the FFL principle.Yixiao ZhangGabriella AngiulliBoris MartinacCharles D. CoxThomas WalzElsevierarticleMechanosensitive channelsSingle-particle cryo-electron microscopyElectrophysiologyBeta-cyclodextrinBiology (General)QH301-705.5ENJournal of Structural Biology: X, Vol 5, Iss , Pp 100053- (2021)
institution DOAJ
collection DOAJ
language EN
topic Mechanosensitive channels
Single-particle cryo-electron microscopy
Electrophysiology
Beta-cyclodextrin
Biology (General)
QH301-705.5
spellingShingle Mechanosensitive channels
Single-particle cryo-electron microscopy
Electrophysiology
Beta-cyclodextrin
Biology (General)
QH301-705.5
Yixiao Zhang
Gabriella Angiulli
Boris Martinac
Charles D. Cox
Thomas Walz
Cyclodextrins for structural and functional studies of mechanosensitive channels
description Mechanosensitive (MS) channels that are activated by the ‘force-from-lipids’ (FFL) principle rest in the membrane in a closed state but open a transmembrane pore in response to changes in the transmembrane pressure profile. The molecular implementations of the FFL principle vary widely between different MS channel families. The function of MS channels is often studied by patch-clamp electrophysiology, in which mechanical force or amphipathic molecules are used to activate the channels. Structural studies of MS channels in states other than the closed resting state typically relied on the use of mutant channels. Cyclodextrins (CDs) were recently introduced as a relatively easy and convenient approach to generate membrane tension. The principle is that CDs chelate hydrophobic molecules and can remove lipids from membranes, thus forcing the remaining lipids to cover more surface area and creating tension for membrane proteins residing in the membranes. CDs can be used to study the structure of MS channels in a membrane under tension by using single-particle cryo-electron microscopy to image the channels in nanodiscs after incubation with CDs as well as to characterize the function of MS channels by using patch-clamp electrophysiology to record the effect of CDs on channels inserted into membrane patches excised from proteoliposomes. Importantly, because incubation of membrane patches with CDs results in the activation of MscL, an MS channel that opens only shortly before membrane rupture, CD-mediated lipid removal appears to generate sufficient force to open most if not all types of MS channels that follow the FFL principle.
format article
author Yixiao Zhang
Gabriella Angiulli
Boris Martinac
Charles D. Cox
Thomas Walz
author_facet Yixiao Zhang
Gabriella Angiulli
Boris Martinac
Charles D. Cox
Thomas Walz
author_sort Yixiao Zhang
title Cyclodextrins for structural and functional studies of mechanosensitive channels
title_short Cyclodextrins for structural and functional studies of mechanosensitive channels
title_full Cyclodextrins for structural and functional studies of mechanosensitive channels
title_fullStr Cyclodextrins for structural and functional studies of mechanosensitive channels
title_full_unstemmed Cyclodextrins for structural and functional studies of mechanosensitive channels
title_sort cyclodextrins for structural and functional studies of mechanosensitive channels
publisher Elsevier
publishDate 2021
url https://doaj.org/article/47ab7ce7f62e47e98fe15b59081ccb28
work_keys_str_mv AT yixiaozhang cyclodextrinsforstructuralandfunctionalstudiesofmechanosensitivechannels
AT gabriellaangiulli cyclodextrinsforstructuralandfunctionalstudiesofmechanosensitivechannels
AT borismartinac cyclodextrinsforstructuralandfunctionalstudiesofmechanosensitivechannels
AT charlesdcox cyclodextrinsforstructuralandfunctionalstudiesofmechanosensitivechannels
AT thomaswalz cyclodextrinsforstructuralandfunctionalstudiesofmechanosensitivechannels
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