Home LiteratureArticle Details
PMID: 26551077 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The role of lipids in mechanosensation.

Nature structural & molecular biology ·Vol. 22 ·No. 12 ·2015-12-00 ·Pages 991-8

Pliotas C, Dahl AC, Rasmussen T, Mahendran KR, Smith TK, Marius P, Gault J, Banda T, Rasmussen A, Miller S, Robinson CV, Bayley H, Sansom MS, Booth IR, Naismith JH

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.

MeSH Terms
Biophysical Phenomena Crystallography, X-Ray Escherichia coli/chemistry,metabolism,physiology Escherichia coli Proteins/chemistry,isolation & purification,metabolism Ion Channels/chemistry,isolation & purification,metabolism Mechanotransduction, Cellular Models, Molecular Molecular Dynamics Simulation Phospholipids/metabolism Protein Conformation
Chemicals
Escherichia coli Proteins Ion Channels MscS protein, E coli Phospholipids
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Pliotas Christos
Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, UK.
Dahl A Caroline E
Department of Biochemistry, University of Oxford, Oxford, UK.
Rasmussen Tim
Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Mahendran Kozhinjampara R
Department of Chemistry, University of Oxford, Oxford, UK.
Smith Terry K
Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, UK.
Marius Phedra
Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, UK.
Gault Joseph
Department of Chemistry, University of Oxford, Oxford, UK.
Banda Thandiwe
Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Rasmussen Akiko
Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Miller Samantha
Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Robinson Carol V
Department of Chemistry, University of Oxford, Oxford, UK.
Bayley Hagan
Department of Chemistry, University of Oxford, Oxford, UK.
Sansom Mark S P
Department of Biochemistry, University of Oxford, Oxford, UK.
Booth Ian R
Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK. | Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
Naismith James H
Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, UK. | State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China.
References (81)
81 references, click to expand
  1. Pivotal role of the glycine-rich TM3 helix in gating the MscS mechanosensitive channel.
    Nat Struct Mol Biol. 2005 Feb;12(2):113-9 PMID: 15665866
  2. Physical principles underlying the transduction of bilayer deformation forces during mechanosensitive channel gating.
    Nat Struct Biol. 2002 Sep;9(9):696-703 PMID: 12172537
  3. Energetic and spatial parameters for gating of the bacterial large conductance mechanosensitive channel, MscL.
    J Gen Physiol. 1999 Apr;113(4):525-40 PMID: 10102934
  4. Two types of mechanosensitive channels in the Escherichia coli cell envelope: solubilization and functional reconstitution.
    Biophys J. 1993 Jul;65(1):177-83 PMID: 7690260
  5. Quantification of free cysteines in membrane and soluble proteins using a fluorescent dye and thermal unfolding.
    Nat Protoc. 2013 Nov;8(11):2090-7 PMID: 24091556
  6. Water dynamics and dewetting transitions in the small mechanosensitive channel MscS.
    Biophys J. 2004 May;86(5):2883-95 PMID: 15111405
  7. Structural basis for self-assembly of a cytolytic pore lined by protein and lipid.
    Nat Commun. 2015;6:6337 PMID: 25716479
  8. Two families of mechanosensitive channel proteins.
    Microbiol Mol Biol Rev. 2003 Mar;67(1):66-85, table of contents PMID: 12626684
  9. Tryptophan in the pore of the mechanosensitive channel MscS: assessment of pore conformations by fluorescence spectroscopy.
    J Biol Chem. 2010 Feb 19;285(8):5377-84 PMID: 20037156
  10. Assessment of potential stimuli for mechano-dependent gating of MscL: effects of pressure, tension, and lipid headgroups.
    Biochemistry. 2005 Sep 13;44(36):12239-44 PMID: 16142922
  11. Pressure-sensitive ion channel in Escherichia coli.
    Proc Natl Acad Sci U S A. 1987 Apr;84(8):2297-301 PMID: 2436228
  12. Better models by discarding data?
    Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1215-22 PMID: 23793147
  13. Lipid composition of membranes of Escherichia coli by liquid chromatography/tandem mass spectrometry using negative electrospray ionization.
    Rapid Commun Mass Spectrom. 2007;21(11):1721-8 PMID: 17477452
  14. CASTp: Computed Atlas of Surface Topography of proteins.
    Nucleic Acids Res. 2003 Jul 1;31(13):3352-5 PMID: 12824325
  15. The structure of an open form of an E. coli mechanosensitive channel at 3.45 A resolution.
    Science. 2008 Aug 29;321(5893):1179-83 PMID: 18755969
  16. A cholate-dilution procedure for the reconstitution of the Ca++ pump, 32Pi--ATP exchange, and oxidative phosphorylation.
    FEBS Lett. 1975 Sep 1;57(1):14-8 PMID: 1175773
  17. Open channel structure of MscL and the gating mechanism of mechanosensitive channels.
    Nature. 2002 Aug 29;418(6901):942-8 PMID: 12198539
  18. Physical mechanism for gating and mechanosensitivity of the human TRAAK K+ channel.
    Nature. 2014 Dec 4;516(7529):126-30 PMID: 25471887
  19. From Coarse Grained to Atomistic: A Serial Multiscale Approach to Membrane Protein Simulations.
    J Chem Theory Comput. 2011 Apr 12;7(4):1157-66 PMID: 26606363
  20. Mechanosensitive channels: what can they do and how do they do it?
    Structure. 2011 Oct 12;19(10):1356-69 PMID: 22000509
  21. Bacterial mechanosensitive channels: progress towards an understanding of their roles in cell physiology.
    Curr Opin Microbiol. 2014 Apr;18:16-22 PMID: 24607989
  22. Gating the bacterial mechanosensitive channel MscL invivo.
    Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5643-8 PMID: 11960017
  23. Bacterial mechanosensitive channels as a paradigm for mechanosensory transduction.
    Cell Physiol Biochem. 2011;28(6):1051-60 PMID: 22178995
  24. Mechanosensitive channels and bacterial cell wall integrity: does life end with a bang or a whimper?
    J R Soc Interface. 2014 Feb 6;11(91):20130850 PMID: 24258154
  25. Detergent-mediated reconstitution of membrane proteins.
    Biochemistry. 1998 Nov 17;37(46):16410-5 PMID: 9819233
  26. Mechanosensitive channels in microbes.
    Annu Rev Microbiol. 2010;64:313-29 PMID: 20825352
  27. Piezo channels: from structure to function.
    Pflugers Arch. 2015 Jan;467(1):95-9 PMID: 25037583
  28. Linking crystallographic model and data quality.
    Science. 2012 May 25;336(6084):1030-3 PMID: 22628654
  29. Open and shut: crystal structures of the dodecylmaltoside solubilized mechanosensitive channel of small conductance from Escherichia coli and Helicobacter pylori at 4.4 Å and 4.1 Å resolutions.
    Protein Sci. 2013 Apr;22(4):502-9 PMID: 23339071
  30. Protection of Escherichia coli cells against extreme turgor by activation of MscS and MscL mechanosensitive channels: identification of genes required for MscS activity.
    EMBO J. 1999 Apr 1;18(7):1730-7 PMID: 10202137
  31. Lipidomic analysis of bloodstream and procyclic form Trypanosoma brucei.
    Parasitology. 2010 Aug;137(9):1357-92 PMID: 20602846
  32. Conformational state of the MscS mechanosensitive channel in solution revealed by pulsed electron-electron double resonance (PELDOR) spectroscopy.
    Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):E2675-82 PMID: 23012406
  33. Purification of the small mechanosensitive channel of Escherichia coli (MscS): the subunit structure, conduction, and gating characteristics in liposomes.
    Biophys J. 2002 Jul;83(1):290-8 PMID: 12080120
  34. Fluorescence quenching methods to study lipid-protein interactions.
    Curr Protoc Protein Sci. 2006 Sep;Chapter 19:Unit 19.12 PMID: 18429301
  35. Selectivity mechanism of the mechanosensitive channel MscS revealed by probing channel subconducting states.
    Nat Commun. 2013;4:2137 PMID: 23842527
  36. Feeling the hidden mechanical forces in lipid bilayer is an original sense.
    Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):7898-905 PMID: 24850861
  37. PoreWalker: a novel tool for the identification and characterization of channels in transmembrane proteins from their three-dimensional structure.
    PLoS Comput Biol. 2009 Jul;5(7):e1000440 PMID: 19609355
  38. Membrane proteins bind lipids selectively to modulate their structure and function.
    Nature. 2014 Jun 5;510(7503):172-5 PMID: 24899312
  39. Bacterial mechanosensitive channels--MscS: evolution's solution to creating sensitivity in function.
    Annu Rev Biophys. 2012;41:157-77 PMID: 22404681
  40. Gating transitions in bacterial ion channels measured at 3 microns resolution.
    J Gen Physiol. 2004 Aug;124(2):151-61 PMID: 15277576
  41. Mechanistic basis for low threshold mechanosensitivity in voltage-dependent K+ channels.
    Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10352-7 PMID: 22675122
  42. Eukaryotic mechanosensitive channels.
    Annu Rev Biophys. 2010;39:111-37 PMID: 20192782
  43. The force-from-lipid (FFL) principle of mechanosensitivity, at large and in elements.
    Pflugers Arch. 2015 Jan;467(1):27-37 PMID: 24888690
  44. Crystal structure of the human two-pore domain potassium channel K2P1.
    Science. 2012 Jan 27;335(6067):432-6 PMID: 22282804
  45. Formation of bimolecular membranes from lipid monolayers and a study of their electrical properties.
    Proc Natl Acad Sci U S A. 1972 Dec;69(12):3561-6 PMID: 4509315
  46. Structure, dynamics and composition of the lipid-protein interface. Perspectives from spin-labelling.
    Biochim Biophys Acta. 1998 Nov 10;1376(3):267-96 PMID: 9804973
  47. Lipid bilayer pressure profiles and mechanosensitive channel gating.
    Biophys J. 2004 Jun;86(6):3496-509 PMID: 15189849
  48. A tandem mass spectrometer for improved transmission and analysis of large macromolecular assemblies.
    Anal Chem. 2002 Mar 15;74(6):1402-7 PMID: 11922310
  49. Lipids in membrane protein structures.
    Biochim Biophys Acta. 2004 Nov 3;1666(1-2):2-18 PMID: 15519305
  50. Emerging roles for lipids in shaping membrane-protein function.
    Nature. 2009 May 21;459(7245):379-85 PMID: 19458714
  51. Mechanosensitive channel MscS in the open state: modeling of the transition, explicit simulations, and experimental measurements of conductance.
    J Gen Physiol. 2008 Jul;132(1):67-83 PMID: 18591417
  52. Sensing and responding to membrane tension: the bacterial MscL channel as a model system.
    Biophys J. 2012 Jul 18;103(2):169-74 PMID: 22853893
  53. The role of tryptophan residues in the function and stability of the mechanosensitive channel MscS from Escherichia coli.
    Biochemistry. 2007 Sep 25;46(38):10899-908 PMID: 17718516
  54. VMD: visual molecular dynamics.
    J Mol Graph. 1996 Feb;14(1):33-8, 27-8 PMID: 8744570
  55. How to measure and analyze tryptophan fluorescence in membranes properly, and why bother?
    Anal Biochem. 2000 Oct 15;285(2):235-45 PMID: 11017708
  56. Determining the stoichiometry and interactions of macromolecular assemblies from mass spectrometry.
    Nat Protoc. 2007;2(3):715-26 PMID: 17406634
  57. A structural mechanism for MscS gating in lipid bilayers.
    Science. 2008 Aug 29;321(5893):1210-4 PMID: 18755978
  58. Biological membranes: the importance of molecular detail.
    Trends Biochem Sci. 2011 Sep;36(9):493-500 PMID: 21855348
  59. A rapid method of total lipid extraction and purification.
    Can J Biochem Physiol. 1959 Aug;37(8):911-7 PMID: 13671378
  60. Transbilayer distribution of bromine in fluid bilayers containing a specifically brominated analogue of dioleoylphosphatidylcholine.
    Biochemistry. 1991 Jul 16;30(28):6997-7008 PMID: 2069956
  61. YbdG in Escherichia coli is a threshold-setting mechanosensitive channel with MscM activity.
    Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12664-9 PMID: 20616037
  62. The CCP4 suite: programs for protein crystallography.
    Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3 PMID: 15299374
  63. Observations on the critical micellar concentration of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine and a series of its homologs and analogs.
    Chem Phys Lipids. 1984 May;35(1):49-62 PMID: 6744496
  64. Differential effects of lipids and lyso-lipids on the mechanosensitivity of the mechanosensitive channels MscL and MscS.
    Proc Natl Acad Sci U S A. 2012 May 29;109(22):8770-5 PMID: 22586095
  65. Structure and molecular mechanism of an anion-selective mechanosensitive channel of small conductance.
    Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):18180-5 PMID: 23074248
  66. Straightening and sequential buckling of the pore-lining helices define the gating cycle of MscS.
    Nat Struct Mol Biol. 2007 Dec;14(12):1141-9 PMID: 18037888
  67. Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel.
    Science. 2012 Jan 27;335(6067):436-41 PMID: 22282805
  68. Probing the structure of the mechanosensitive channel of small conductance in lipid bilayers with pulsed electron-electron double resonance.
    Biophys J. 2014 Feb 18;106(4):834-42 PMID: 24559986
  69. A possible unifying principle for mechanosensation.
    Nature. 2005 Aug 4;436(7051):647-54 PMID: 16079835
  70. State-stabilizing Interactions in Bacterial Mechanosensitive Channel Gating and Adaptation.
    J Biol Chem. 2009 Jul 17;284(29):19153-7 PMID: 19383606
  71. The PDB_REDO server for macromolecular structure model optimization.
    IUCrJ. 2014 May 30;1(Pt 4):213-20 PMID: 25075342
  72. Molecular dynamics study of gating in the mechanosensitive channel of small conductance MscS.
    Biophys J. 2004 Nov;87(5):3050-65 PMID: 15339798
  73. The MARTINI Coarse-Grained Force Field: Extension to Proteins.
    J Chem Theory Comput. 2008 May;4(5):819-34 PMID: 26621095
  74. Coarse-grained MD simulations of membrane protein-bilayer self-assembly.
    Structure. 2008 Apr;16(4):621-30 PMID: 18400182
  75. Reevaluation of the PPAR-beta/delta ligand binding domain model reveals why it exhibits the activated form.
    Mol Cell. 2006 Jan 6;21(1):1-2 PMID: 16387648
  76. Crystal structure of Escherichia coli MscS, a voltage-modulated and mechanosensitive channel.
    Science. 2002 Nov 22;298(5598):1582-7 PMID: 12446901
  77. Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K+ channels.
    Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):3614-9 PMID: 24550493
  78. Physiological analysis of bacterial mechanosensitive channels.
    Methods Enzymol. 2007;428:47-61 PMID: 17875411
  79. Structure and mechanism in prokaryotic mechanosensitive channels.
    Curr Opin Struct Biol. 2003 Aug;13(4):432-42 PMID: 12948773
  80. GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation.
    J Chem Theory Comput. 2008 Mar;4(3):435-47 PMID: 26620784
  81. Stiffened lipid platforms at molecular force foci.
    Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):4886-92 PMID: 23476066
Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.3120
Published
2015-12-00
Epub
2015-00-09
Pages
991-8
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC4675090
Subset
IM
Grants
Wellcome Trust · WT092552MA · United Kingdom
Wellcome Trust · 100209 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/H017402/1 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/H017917/1 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/J009784/1 · United Kingdom
Wellcome Trust · 092552 · United Kingdom
Wellcome Trust · 093228 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/I019855/1 · United Kingdom
Wellcome Trust · WT100209MA · United Kingdom
Databases
PDB
5AJI
External Links
PubMed source DOI: 10.1038/nsmb.3120 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2