The role of lipids in mechanosensation
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Date
12/2015Author
Grant ID
092552/C/10/Z
100209/Z/12/Z
BB/H017917/1
093228/Z/10/Z
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Show full item recordAbstract
The ability of proteins to sense membrane tension is pervasive in biology. A higher-resolution structure of the Escherichia coli small-conductance mechanosensitive channel MscS identifies alkyl chains inside pockets formed by the transmembrane helices (TMs). Purified MscS contains E. coli lipids, and fluorescence quenching demonstrates that phospholipid acyl chains exchange between bilayer and TM pockets. Molecular dynamics and biophysical analyses show that the volume of the pockets and thus the number of lipid acyl chains within them decreases upon channel opening. Phospholipids with one acyl chain per head group (lysolipids) displace normal phospholipids (with two acyl chains) from MscS pockets and trigger channel opening. We propose that the extent of acyl-chain interdigitation in these pockets determines the conformation of MscS. When interdigitation is perturbed by increased membrane tension or by lysolipids, the closed state becomes unstable, and the channel gates.
Citation
Pliotas , C , Dahl , A C E , Rasmussen , T , Mahendran , K R , Smith , T K , Marius , P , Gault , J , Banda , T , Rasmussen , A , Miller , S , Robinson , C V , Bayley , H , Sansom , M S P , Booth , I R & Naismith , J 2015 , ' The role of lipids in mechanosensation ' , Nature Structural and Molecular Biology , vol. 22 , no. 12 , pp. 991-998 . https://doi.org/10.1038/nsmb.3120
Publication
Nature Structural and Molecular Biology
Status
Peer reviewed
ISSN
1545-9993Type
Journal article
Rights
Copyright 2015 the Authors. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at: https://dx.doi.org/10.1038/nsmb.3120
Description
This work was supported by Wellcome Trust grants WT092552MA (J.H.N. and I.R.B.), Senior Investigator Award WT100209MA (J.H.N.), 093228 (T.K.S.) and 092970 (M.S.P.S.), and Biotechnology and Biological Sciences Research Council grants BB/I019855/1 (M.S.P.S.), BB/H017917/1 (J.H.N. and I.R.B.) and BB/J009784/1 (H.B.). I.R.B. is supported as a Leverhulme Emeritus Fellow. J.H.N. is supported as a Royal Society Wolfson Merit Award holder and as a 1000 Talent Scholar at Sichuan University. A.C.E.D. was supported by an Engineering and Physical Sciences Research Council Systems Biology Doctoral Training Centre student fellowship.Collections
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