Academic Journal
Προβολή σε EDS

Atomic structure and dynamics of the mechanosensitive channel MscL from Escherichia coli by cryo-EM and solid-state NMR.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Atomic structure and dynamics of the mechanosensitive channel MscL from Escherichia coli by cryo-EM and solid-state NMR.
Συγγραφείς: Xiao T; Research Unit Molecular Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Kovinko A; Research Unit Molecular Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Shi C; Research Unit Molecular Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.; Hefei National Research Center for Interdisciplinary Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, China., Sawczyc H; Research Unit Molecular Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Qoraj D; Research Unit Molecular Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Öster C; Research Unit Molecular Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Sprink T; Core Facility for Cryo-Electron Microscopy of the Charité-Universitätsmedizin Berlin at the Max Delbrück Center, Berlin, Germany.; Max Delbrück Center for Molecular Medicine, Technology Platform Cryo-EM, Berlin, Germany., Ketzel AF; Research Unit Structural Chemistry and Computational Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.; Institute of Chemistry, Technische Universität Berlin, Berlin, Germany., Lange S; Research Unit Molecular Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Kosteletos S; Research Unit Molecular Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Sun H; Research Unit Structural Chemistry and Computational Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.; Institute of Chemistry, Technische Universität Berlin, Berlin, Germany., Roderer D; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Chen S; Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Lange A; Research Unit Molecular Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.; Institute of Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
Πηγή: Science advances [Sci Adv] 2026 Oct 09; Vol. 12 (41), pp. eaei0096. Date of Electronic Publication: 2026 Oct 07.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE
Imprint Name(s): Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]-
Ιατρικοί όροι (MeSH): Escherichia coli Proteins*/chemistry , Escherichia coli Proteins*/genetics , Escherichia coli Proteins*/metabolism , Ion Channels*/chemistry , Ion Channels*/genetics , Ion Channels*/metabolism , Ion Channels*/ultrastructure , Escherichia coli*/metabolism , Escherichia coli*/genetics , Cryoelectron Microscopy* , Mechanotransduction, Cellular*, Liposomes/chemistry ; Protein Conformation ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Mutation
Περίληψη: Mechanosensitive channels are central to cellular responses to membrane tension, yet the structural basis of their gating remains incompletely understood. Here, we determine the structures of wild-type and Gly22→Ser (G22S) mutants of MscL from Escherichia coli (EcMscL) by cryogenic electron microscopy (cryo-EM) in peptide-based lipid nanodiscs and complement them with solid-state nuclear magnetic resonance (NMR) measurements in liposomes to capture their dynamics in a native-like membrane environment. The cryo-EM structures reveal a closed conformation, whereas analysis of the low-threshold G22S mutant by NMR uncovers widespread conformational changes in both cytoplasmic and periplasmic regions. These data indicate enhanced dynamics and conformational heterogeneity in the mutant, revealing the early transitions from the closed toward the open state. Together, our results establish a synergistic framework integrating cryo-EM and NMR to resolve both structure and dynamics of mechanosensitive channels, and identify lipid-protein interactions as key determinants of MscL gating and mechanosensitivity. Our study further provides a quantitative benchmark for computational investigations of mechanogating and lays the foundation for the rational design of channels with tunable gating kinetics.
References: Prog Nucl Magn Reson Spectrosc. 2013 Aug;73:1-16. (PMID: 23962882)
J Magn Reson. 2013 May;230:205-11. (PMID: 23558259)
J Biomol NMR. 1995 Nov;6(3):277-93. (PMID: 8520220)
Science. 1998 Dec 18;282(5397):2220-6. (PMID: 9856938)
Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):519-530. (PMID: 29872003)
J Phys Chem B. 2021 Mar 18;125(10):2477-2490. (PMID: 33685127)
J Biol Chem. 1998 Oct 9;273(41):26670-4. (PMID: 9756908)
Biophys J. 2003 Apr;84(4):2357-65. (PMID: 12668444)
Biophys J. 2007 Feb 15;92(4):1233-40. (PMID: 17142294)
J Am Chem Soc. 2026 Jan 14;148(1):1444-1456. (PMID: 41420568)
J Biomol NMR. 2016 Oct;66(2):111-124. (PMID: 27663422)
Biophys J. 2004 Apr;86(4):2113-20. (PMID: 15041651)
J Magn Reson. 2007 Oct;188(2):295-300. (PMID: 17723313)
Nature. 1994 Mar 17;368(6468):265-8. (PMID: 7511799)
Biochemistry. 2008 Apr 8;47(14):4317-28. (PMID: 18341289)
J Cell Biol. 2023 Sep 4;222(9):. (PMID: 37382667)
FASEB J. 2011 Feb;25(2):694-702. (PMID: 21068398)
J Comput Chem. 2011 Jul 30;32(10):2319-27. (PMID: 21500218)
Biophys J. 1993 Dec;65(6):2455-60. (PMID: 7508762)
Biophys J. 2003 Oct;85(4):2087-99. (PMID: 14507677)
J Mol Graph. 1996 Dec;14(6):354-60, 376. (PMID: 9195488)
Int J Mol Sci. 2022 Dec 01;23(23):. (PMID: 36499396)
Bioinformatics. 2015 Apr 15;31(8):1325-7. (PMID: 25505092)
Sci Adv. 2024 May 17;10(20):eadm7907. (PMID: 38758787)
Nat Commun. 2023 Oct 7;14(1):6284. (PMID: 37805510)
J Am Chem Soc. 2025 Sep 24;147(38):34487-34497. (PMID: 40924873)
J Biomol NMR. 2012 Apr;52(4):315-27. (PMID: 22331404)
J Mol Graph. 1996 Feb;14(1):33-8, 27-8. (PMID: 8744570)
Front Chem. 2023 Jun 06;11:1175443. (PMID: 37347044)
Chem Biol. 2015 May 21;22(5):593-603. (PMID: 26000747)
J Mol Biol. 1999 Sep 17;292(2):195-202. (PMID: 10493868)
Nat Commun. 2016 Jun 22;7:11984. (PMID: 27329693)
Nat Methods. 2017 Mar;14(3):290-296. (PMID: 28165473)
Nature. 2021 Feb;590(7846):509-514. (PMID: 33568813)
Biophys J. 2007 Feb 15;92(4):1224-32. (PMID: 17114217)
Proc Natl Acad Sci U S A. 2021 Aug 17;118(33):. (PMID: 34376558)
Biochemistry. 2008 Nov 18;47(46):12175-84. (PMID: 18950196)
Nature. 2001 Feb 8;409(6821):720-4. (PMID: 11217861)
Nat Plants. 2020 Oct;6(10):1219-1224. (PMID: 33020606)
Biochemistry. 2005 Sep 13;44(36):12239-44. (PMID: 16142922)
Biophys J. 1999 Oct;77(4):1960-72. (PMID: 10512816)
JACS Au. 2023 Nov 21;3(12):3412-3423. (PMID: 38155644)
Proc Natl Acad Sci U S A. 2024 Nov 12;121(46):e2407731121. (PMID: 39508769)
Nat Struct Biol. 2002 Sep;9(9):696-703. (PMID: 12172537)
Sci Rep. 2017 Dec 8;7(1):17229. (PMID: 29222414)
Biochim Biophys Acta. 2016 Aug;1861(8 Pt B):847-861. (PMID: 26747646)
Elife. 2019 Dec 27;8:. (PMID: 31880537)
Nature. 2002 Aug 29;418(6901):942-8. (PMID: 12198539)
Trends Microbiol. 1999 Oct;7(10):420-4. (PMID: 10498951)
Curr Opin Struct Biol. 2025 Oct;94:103129. (PMID: 40782689)
J Magn Reson. 2010 May;204(1):155-9. (PMID: 20194040)
J Am Chem Soc. 2025 May 28;147(21):17612-17625. (PMID: 40377170)
FASEB J. 2014 Dec;28(12):5234-41. (PMID: 25223610)
Commun Biol. 2021 Jul 15;4(1):874. (PMID: 34267316)
J Am Chem Soc. 2026 Feb 18;148(6):5909-5915. (PMID: 41641854)
J Am Chem Soc. 2010 Feb 24;132(7):2145-7. (PMID: 20121194)
Nature. 2024 Jun;630(8016):493-500. (PMID: 38718835)
Protein Sci. 2016 Nov;25(11):1954-1964. (PMID: 27530280)
J Mol Biol. 2014 Feb 6;426(3):735-51. (PMID: 24513108)
Protein Sci. 2021 Jan;30(1):70-82. (PMID: 32881101)
J Am Chem Soc. 2026 Mar 11;148(9):9433-9448. (PMID: 41730721)
Microbiol Mol Biol Rev. 2020 Jan 15;84(1):. (PMID: 31941768)
Eur Biophys J. 2005 Jul;34(5):403-12. (PMID: 15812636)
Nat Struct Biol. 2002 Sep;9(9):704-10. (PMID: 12172538)
Structure. 2022 Apr 7;30(4):608-622.e5. (PMID: 34986323)
EMBO J. 1999 Apr 1;18(7):1730-7. (PMID: 10202137)
PLoS One. 2014 Dec 01;9(12):e113947. (PMID: 25437007)
Nature. 2022 Apr;604(7905):377-383. (PMID: 35388220)
Biochim Biophys Acta. 2001 Oct 1;1514(2):165-9. (PMID: 11557017)
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501. (PMID: 20383002)
J Am Chem Soc. 2025 Oct 1;147(39):35718-35729. (PMID: 40974309)
Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11471-5. (PMID: 9736761)
J Am Chem Soc. 2026 Mar 04;148(8):8554-8566. (PMID: 41702852)
J Magn Reson. 2001 May;150(1):81-99. (PMID: 11330986)
J Am Chem Soc. 2024 Nov 20;146(46):31472-31485. (PMID: 39503730)
Nat Rev Mol Cell Biol. 2024 Nov;25(11):886-903. (PMID: 39251883)
FASEB J. 2009 Jul;23(7):2197-204. (PMID: 19261722)
Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):. (PMID: 34475213)
Nature. 2005 Aug 4;436(7051):647-54. (PMID: 16079835)
Biophys J. 2006 Mar 15;90(6):1992-8. (PMID: 16387769)
PLoS One. 2017 Aug 31;12(8):e0183822. (PMID: 28859093)
J Am Chem Soc. 2025 Apr 02;147(13):11117-11131. (PMID: 40106808)
Nat Commun. 2021 Jul 13;12(1):4272. (PMID: 34257293)
Channels (Austin). 2012 Jul-Aug;6(4):317-31. (PMID: 23146938)
J Am Chem Soc. 2022 Sep 28;144(38):17336-17340. (PMID: 36074981)
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21. (PMID: 20124702)
Nat Commun. 2025 Aug 23;16(1):7881. (PMID: 40849500)
Protein Sci. 2013 Nov;22(11):1592-601. (PMID: 24038743)
J Chem Inf Model. 2025 Jun 23;65(12):6129-6143. (PMID: 40471653)
Biophys J. 2001 Aug;81(2):917-36. (PMID: 11463635)
Sci Adv. 2024 Oct 4;10(40):eadq3115. (PMID: 39356759)
Sci Rep. 2018 Oct 1;8(1):14566. (PMID: 30275500)
J Am Chem Soc. 2007 Aug 22;129(33):10195-200. (PMID: 17663552)
J Biol Chem. 2000 Oct 6;275(40):31121-7. (PMID: 10846181)
Angew Chem Int Ed Engl. 2026 Mar 02;65(10):e14067. (PMID: 41607018)
Magn Reson Chem. 2020 May;58(5):445-465. (PMID: 31691361)
Structure. 2024 Jun 6;32(6):739-750.e4. (PMID: 38521071)
Nat Commun. 2025 Jan 22;16(1):935. (PMID: 39843904)
Front Chem. 2023 Mar 15;11:1162412. (PMID: 37021145)
Nucleic Acids Res. 2003 Jul 1;31(13):3320-3. (PMID: 12824317)
JACS Au. 2023 Oct 11;3(10):2763-2771. (PMID: 37885577)
J Biomol NMR. 2025 Mar;79(1):25-34. (PMID: 39841396)
Biophys J. 2012 Jul 18;103(2):169-74. (PMID: 22853893)
Biophys J. 2004 May;86(5):2846-61. (PMID: 15111402)
Proc Natl Acad Sci U S A. 2015 Aug 25;112(34):10726-31. (PMID: 26261325)
Biophys J. 1997 Oct;73(4):1925-31. (PMID: 9336188)
Chemistry. 2023 Jan 12;29(3):e202202106. (PMID: 36251739)
Sci Adv. 2024 Jan 26;10(4):eadj0384. (PMID: 38266078)
J Phys Chem Lett. 2024 Jan 11;15(1):175-179. (PMID: 38153203)
J Struct Biol. 2012 Dec;180(3):519-30. (PMID: 23000701)
Substance Nomenclature: 0 (MscL protein, E coli)
0 (Escherichia coli Proteins)
0 (Ion Channels)
0 (Liposomes)
Entry Date(s): Date Created: 20261007 Date Completed: 20261007 Latest Revision: 20261009
Update Code: 20261009
PubMed Central ID: PMC13644787
DOI: 10.1126/sciadv.aei0096
PMID: 42842685
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2375-2548
DOI:10.1126/sciadv.aei0096