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PMID: 18755978 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

A structural mechanism for MscS gating in lipid bilayers.

Science (New York, N.Y.) ·Vol. 321 ·No. 5893 ·2008-08-29 ·Pages 1210-4

Vásquez V, Sotomayor M, Cordero-Morales J, Schulten K, Perozo E

Abstract

The mechanosensitive channel of small conductance (MscS) is a key determinant in the prokaryotic response to osmotic challenges. We determined the structural rearrangements associated with MscS activation in membranes, using functorial measurements, electron paramagnetic resonance spectroscopy, and computational analyses. MscS was trapped in its open conformation after the transbilayer pressure profile was modified through the asymmetric incorporation of lysophospholipids. The transition from the closed to the open state is accompanied by the downward tilting of the transmembrane TM1-TM2 hairpin and by the expansion, tilt, and rotation of the TM3 helices. These movements expand the permeation pathway, leading to an increase in accessibility to water around TM3. Our open MscS model is compatible with single-channel conductance measurements and supports the notion that helix tilting is associated with efficient pore widening in mechanosensitive channels.

MeSH Terms
Electron Spin Resonance Spectroscopy Escherichia coli Proteins/chemistry,genetics,physiology Ion Channel Gating Ion Channels/chemistry,genetics,physiology Lipid Bilayers Lysophosphatidylcholines Micelles Models, Molecular Mutant Proteins/chemistry,metabolism Patch-Clamp Techniques Pressure Protein Conformation Protein Structure, Secondary
Chemicals
Escherichia coli Proteins Ion Channels Lipid Bilayers Lysophosphatidylcholines Micelles MscS protein, E coli Mutant Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Vásquez Valeria
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA.
Sotomayor Marcos
Cordero-Morales Julio
Schulten Klaus
Perozo Eduardo
References (36)
36 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. Lysophospholipids open the two-pore domain mechano-gated K(+) channels TREK-1 and TRAAK.
    J Biol Chem. 2000 Apr 7;275(14):10128-33 PMID: 10744694
  3. The gating mechanism of the large mechanosensitive channel MscL.
    Nature. 2001 Feb 8;409(6821):720-4 PMID: 11217861
  4. A large iris-like expansion of a mechanosensitive channel protein induced by membrane tension.
    Nat Struct Biol. 2002 Sep;9(9):704-10 PMID: 12172538
  5. 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
  6. Site-directed spin-labeling analysis of reconstituted Mscl in the closed state.
    J Gen Physiol. 2001 Aug;118(2):193-206 PMID: 11479346
  7. Voltage-dependent hydration and conduction properties of the hydrophobic pore of the mechanosensitive channel of small conductance.
    Biophys J. 2006 May 15;90(10):3555-69 PMID: 16500980
  8. An optimized purification and reconstitution method for the MscS channel: strategies for spectroscopical analysis.
    Biochemistry. 2007 Jun 12;46(23):6766-73 PMID: 17500538
  9. Mechanosensitive ion channels of E. coli activated by amphipaths.
    Nature. 1990 Nov 15;348(6298):261-3 PMID: 1700306
  10. Two families of mechanosensitive channel proteins.
    Microbiol Mol Biol Rev. 2003 Mar;67(1):66-85, table of contents PMID: 12626684
  11. Lipid-protein interaction of the MscS mechanosensitive channel examined by scanning mutagenesis.
    Biophys J. 2006 Oct 15;91(8):2874-81 PMID: 16861270
  12. Water dynamics and dewetting transitions in the small mechanosensitive channel MscS.
    Biophys J. 2004 May;86(5):2883-95 PMID: 15111405
  13. TRP channels in mechanosensation: direct or indirect activation?
    Nat Rev Neurosci. 2007 Jul;8(7):510-21 PMID: 17585304
  14. Loss-of-function mutations at the rim of the funnel of mechanosensitive channel MscL.
    Biophys J. 2004 Apr;86(4):2113-20 PMID: 15041651
  15. Gating of MscL studied by steered molecular dynamics.
    Biophys J. 2003 Oct;85(4):2087-99 PMID: 14507677
  16. HOLE: a program for the analysis of the pore dimensions of ion channel structural models.
    J Mol Graph. 1996 Dec;14(6):354-60, 376 PMID: 9195488
  17. The "dashpot" mechanism of stretch-dependent gating in MscS.
    J Gen Physiol. 2005 Feb;125(2):143-54 PMID: 15657299
  18. 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
  19. Molecular dynamics study of gating in the mechanosensitive channel of small conductance MscS.
    Biophys J. 2004 Nov;87(5):3050-65 PMID: 15339798
  20. Physical principles underlying the transduction of bilayer deformation forces during mechanosensitive channel gating.
    Nat Struct Biol. 2002 Sep;9(9):696-703 PMID: 12172537
  21. Domain organization of the MscS mechanosensitive channel of Escherichia coli.
    EMBO J. 2003 Jan 2;22(1):36-46 PMID: 12505982
  22. Open channel structure of MscL and the gating mechanism of mechanosensitive channels.
    Nature. 2002 Aug 29;418(6901):942-8 PMID: 12198539
  23. Structural determinants of MscL gating studied by molecular dynamics simulations.
    Biophys J. 2001 May;80(5):2074-81 PMID: 11325711
  24. Electrostatic properties of the mechanosensitive channel of small conductance MscS.
    Biophys J. 2006 May 15;90(10):3496-510 PMID: 16513774
  25. Mechanosensitive channels in prokaryotes.
    Cell Physiol Biochem. 2001;11(2):61-76 PMID: 11275684
  26. TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction.
    Neuron. 2006 Apr 20;50(2):277-89 PMID: 16630838
  27. Revisiting TRPC1 and TRPC6 mechanosensitivity.
    Pflugers Arch. 2008 Mar;455(6):1097-103 PMID: 17957383
  28. Ion conduction through MscS as determined by electrophysiology and simulation.
    Biophys J. 2007 Feb 1;92(3):886-902 PMID: 17114233
  29. 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
  30. Actin stress fibers transmit and focus force to activate mechanosensitive channels.
    J Cell Sci. 2008 Feb 15;121(Pt 4):496-503 PMID: 18230647
  31. Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel.
    Science. 1998 Dec 18;282(5397):2220-6 PMID: 9856938
  32. Crystal structure of Escherichia coli MscS, a voltage-modulated and mechanosensitive channel.
    Science. 2002 Nov 22;298(5598):1582-7 PMID: 12446901
  33. Three-dimensional architecture of membrane-embedded MscS in the closed conformation.
    J Mol Biol. 2008 Apr 18;378(1):55-70 PMID: 18343404
  34. Pressure-sensitive ion channel in Escherichia coli.
    Proc Natl Acad Sci U S A. 1987 Apr;84(8):2297-301 PMID: 2436228
  35. Spin labeled cysteines as sensors for protein-lipid interaction and conformation in rhodopsin.
    Photochem Photobiol. 1992 Dec;56(6):1019-33 PMID: 1492127
  36. Voltage-independent adaptation of mechanosensitive channels in Escherichia coli protoplasts.
    J Membr Biol. 1998 Aug 1;164(3):253-62 PMID: 9691118
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1159674
Published
2008-08-29
Pages
1210-4
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2897165
Subset
IM
Grants
NIGMS NIH HHS · R01 GM067887-05 · United States
NCRR NIH HHS · P41 RR005969 · United States
NIGMS NIH HHS · R01 GM063617 · United States
NCRR NIH HHS · P41-RR05969 · United States
NIGMS NIH HHS · 1 R01 GM067887 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01 GM067887 · United States
NCRR NIH HHS · P41 RR005969-19 · United States
NIGMS NIH HHS · GM063617 · United States
Corrections
CommentIn
PMID: 18755963
External Links
PubMed source DOI: 10.1126/science.1159674 PMC Full Text View journal details
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