CaltechAUTHORS
  A Caltech Library Service

The role of lipids in mechanosensation

Pliotas, Christos and Dahl, A. Caroline E. and Rasmussen, Tim and Mahendran, Kozhinjampara R. and Smith, Terry K. and Marius, Phedra and Gault, Joseph and Banda, Thandiwe and Rasmussen, Akiko and Miller, Samantha and Robinson, Carol V. and Bayley, Hagan and Sansom, Mark S. P. and Booth, Ian R. and Naismith, James H. (2015) The role of lipids in mechanosensation. Nature Structural and Molecular Biology, 22 (12). pp. 991-998. ISSN 1545-9993. PMCID PMC4675090. https://resolver.caltech.edu/CaltechAUTHORS:20151116-104333476

[img] PDF - Accepted Version
See Usage Policy.

2079Kb
[img] PDF (Supplementary Text and Figures) - Supplemental Material
See Usage Policy.

4Mb
[img] Video (MPEG) (Video 1: Coarse-grain molecular dynamics image of lipid around protein) - Supplemental Material
See Usage Policy.

6Mb
[img] Video (MPEG) (Video 2: Atomistic molecular dynamics image of lipid around protein) - Supplemental Material
See Usage Policy.

7Mb
[img] Image (JPEG) (Supplementary Figure 1: Additional structural data) - Supplemental Material
See Usage Policy.

106Kb
[img] Image (JPEG) (Supplementary Figure 2: Additional lipid analysis) - Supplemental Material
See Usage Policy.

103Kb
[img] Image (JPEG) (Supplementary Figure 3: Additional molecular dynamics analysis) - Supplemental Material
See Usage Policy.

232Kb
[img] Image (JPEG) (Supplementary Figure 4: Additional data on MscS mutants and the effect of LPC on MscS) - Supplemental Material
See Usage Policy.

154Kb
[img] Image (JPEG) (Supplementary Figure 5: Additional single-molecule data on MscS) - Supplemental Material
See Usage Policy.

181Kb
[img] Image (JPEG) (Supplementary Figure 6: Bromolipids) - Supplemental Material
See Usage Policy.

71Kb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20151116-104333476

Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/nsmb.3120DOIArticle
http://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.3120.htmlPublisherArticle
http://rdcu.be/eUq1PublisherFree ReadCube access
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675090PubMed CentralArticle
Additional Information:© 2015 Nature Publishing Group. Received 9 June; accepted 6 October; published online 9 November 2015. 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.). We acknowledge the Diamond Light Source for beam time. 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. We thank R. Phillips, A. Lee and S. Conway for helpful discussions. These authors contributed equally to this work. Christos Pliotas, A Caroline E Dahl, Tim Rasmussen & Kozhinjampara R Mahendran Author Contributions:C.P. purified and spin-labeled MscS for lipid analysis, single-molecule analysis and crystallization; obtained and analyzed the new crystal structure; and participated in the single-molecule and lipid-analysis experiments. T.R. purified MscS and carried out and analyzed the fluorescence studies including synthesis of brominated lipids. A.C.E.D. wrote the MD-analysis software and performed and analyzed the simulations. K.R.M. performed and analyzed single-molecule experiments. A.R. made mutants of MscS and performed osmotic downshock assays. T.B. assisted in fluorescence experiments. T.K.S. performed lipidomic mass spectrometry. C.V.R. and J.G. carried out native mass spectrometry. P.M. performed TLC experiments. S.M., H.B., M.S.P.S., I.R.B. and J.H.N. conceived and supervised the study. All authors wrote, reviewed and approved the paper. The authors declare no competing financial interests.
Funders:
Funding AgencyGrant Number
Wellcome TrustWT092552MA
Wellcome TrustWT100209MA
Wellcome Trust093228
Wellcome Trust092970
Biotechnology and Biological Sciences Research Council (BBSRC)B/I019855/1
Biotechnology and Biological Sciences Research Council (BBSRC)BB/H017917/1
Biotechnology and Biological Sciences Research Council (BBSRC)BB/J009784/1
Leverhulme TrustUNSPECIFIED
Royal SocietyUNSPECIFIED
Engineering and Physical Sciences Research Council (EPSRC)UNSPECIFIED
Issue or Number:12
PubMed Central ID:PMC4675090
Record Number:CaltechAUTHORS:20151116-104333476
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20151116-104333476
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:62121
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:17 Nov 2015 23:55
Last Modified:03 Oct 2019 09:15

Repository Staff Only: item control page