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Cited by 20Ion channel regulation and functionIon Channels and ReceptorsProtein Structure and Dynamics

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Structure of mechanically activated ion channel OSCA2.3 reveals mobile elements in the transmembrane domain

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Jojoa-Cruz, Sebastian, Burendei, Batuujin, Lee, Wen-Hsin, Ward, Andrew B.·2024·Structure
DOI 10.1016/j.str.2023.11.009PMC PMC10872982

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Abstract

Members of the OSCA/TMEM63 family are mechanically activated ion channels and structures of some OSCA members have revealed the architecture of these channels and structural features that are potentially involved in mechanosensation. However, these structures are all in a similar state and information about the motion of different elements of the structure is limited, preventing a deeper understanding of how these channels work. Here, we used cryoelectron microscopy to determine high-resolution structures of Arabidopsis thaliana OSCA1.2 and OSCA2.3 in peptidiscs. The structure of OSCA1.2 matches previous structures of the same protein in different environments. Yet, in OSCA2.3, the TM6a-TM7 linker adopts a different conformation that constricts the pore on its cytoplasmic side. Furthermore, coevolutionary sequence analysis uncovered a conserved interaction between the TM6a-TM7 linker and the beam-like domain (BLD). Our results reveal conformational heterogeneity and differences in conserved interactions between the TMD and BLD among members of the OSCA family.

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Research works printed but not linked: 84

  1. Haswell, 2011, Mechanosensitive Channels: What Can They Do and How Do They Do It?, Structure, 19, 1356, 10.1016/j.str.2011.09.005 · DOI
  2. Ranade, 2015, Mechanically Activated Ion Channels, Neuron, 87, 1162, 10.1016/j.neuron.2015.08.032 · DOI · Paper page
  3. Hamilton, 2015, Mechanosensitive channel MSL8 regulates osmotic forces during pollen hydration and germination, Science, 350, 438, 10.1126/science.aac6014 · DOI
  4. Basu, 2020, Interactions between the N- and C-termini of the mechanosensitive ion channel AtMSL10 are consistent with a three-step mechanism for activation, J. Exp. Bot., 71, 4020, 10.1093/jxb/eraa192 · DOI
  5. Basu, 2020, The Mechanosensitive Ion Channel MSL10 Potentiates Responses to Cell Swelling in Arabidopsis Seedlings, Curr. Biol., 30, 2716, 10.1016/j.cub.2020.05.015 · DOI
  6. Thor, 2020, The calcium-permeable channel OSCA1.3 regulates plant stomatal immunity, Nature, 585, 569, 10.1038/s41586-020-2702-1 · DOI
  7. Murthy, 2018, OSCA/TMEM63 are an Evolutionarily Conserved Family of Mechanically Activated Ion Channels, Elife, 7, 10.7554/eLife.41844 · DOI
  8. Yuan, 2014, OSCA1 mediates osmotic-stress-evoked Ca2+ increases vital for osmosensing in Arabidopsis, Nature, 514, 367, 10.1038/nature13593 · DOI
  9. Kiyosue, 1994, Cloning of cDNAs for genes that are early-responsive to dehydration stress (ERDs) in Arabidopsis thaliana L.: identification of three ERDs as HSP cognate genes, Plant Mol. Biol., 25, 791, 10.1007/BF00028874 · DOI
  10. Zhai, 2021, Functional analysis of rice OSCA genes overexpressed in the arabidopsis osca1 mutant due to drought and salt stresses, Transgenic Res., 30, 811, 10.1007/s11248-021-00270-x · DOI
  11. Zhai, 2020, Heterogeneous expression of plasma-membrane-localised OsOSCA1.4 complements osmotic sensing based on hyperosmolality and salt stress in Arabidopsis osca1 mutant, Cell Calcium, 91, 10.1016/j.ceca.2020.102261 · DOI
  12. Zhang, 2020, Osmotic stress alters circadian cytosolic Ca(2+) oscillations and OSCA1 is required in circadian gated stress adaptation, Plant Signal. Behav., 15, 10.1080/15592324.2020.1836883 · DOI
  13. Yin, 2021, Genome-wide analysis of OSCA gene family members in Vigna radiata and their involvement in the osmotic response, BMC Plant Biol., 21, 408, 10.1186/s12870-021-03184-2 · DOI
  14. FAO, 2017, The future of food and agriculture–Trends and challenges, Annu. Rep., 296
  15. Cao, 2020, Systematic Analysis of the Maize OSCA Genes Revealing ZmOSCA Family Members Involved in Osmotic Stress and ZmOSCA2.4 Confers Enhanced Drought Tolerance in Transgenic Arabidopsis, Int. J. Mol. Sci., 21, 10.3390/ijms21010351 · DOI
  16. Hou, 2014, DUF221 proteins are a family of osmosensitive calcium-permeable cation channels conserved across eukaryotes, Cell Res., 24, 632, 10.1038/cr.2014.14 · DOI
  17. Li, 2015, Genome-wide survey and expression analysis of the OSCA gene family in rice, BMC Plant Biol., 15, 261, 10.1186/s12870-015-0653-8 · DOI
  18. Hamilton, 2015, United in diversity: mechanosensitive ion channels in plants, Annu. Rev. Plant Biol., 66, 113, 10.1146/annurev-arplant-043014-114700 · DOI
  19. Zhang, 2018, Structure of the mechanosensitive OSCA channels, Nat. Struct. Mol. Biol., 25, 850, 10.1038/s41594-018-0117-6 · DOI
  20. Jojoa-Cruz, 2018, Cryo-EM structure of the mechanically activated ion channel OSCA1.2, Elife, 7, e41845, 10.7554/eLife.41845 · DOI
  21. Liu, 2018, Structure of the hyperosmolality-gated calcium-permeable channel OSCA1.2, Nat. Commun., 9, 5060, 10.1038/s41467-018-07564-5 · DOI
  22. Maity, 2019, Cryo-EM structure of OSCA1.2 from Oryza sativa elucidates the mechanical basis of potential membrane hyperosmolality gating, Proc. Natl. Acad. Sci. USA, 116, 14309, 10.1073/pnas.1900774116 · DOI
  23. Carlson, 2018, The Peptidisc, a simple method for stabilizing membrane proteins in detergent-free solution, Elife, 7, 10.7554/eLife.34085 · DOI
  24. Ridone, 2020, Disruption of membrane cholesterol organization impairs the activity of PIEZO1 channel clusters, J. Gen. Physiol., 152, 10.1085/jgp.201912515 · DOI
  25. Arndt, 2022, Structural basis for the activation of the lipid scramblase TMEM16F, Nat. Commun., 13, 6692, 10.1038/s41467-022-34497-x · DOI
  26. Brunner, 2014, X-ray structure of a calcium-activated TMEM16 lipid scramblase, Nature, 516, 207, 10.1038/nature13984 · DOI
  27. Paulino, 2017, Activation mechanism of the calcium-activated chloride channel TMEM16A revealed by cryo-EM, Nature, 552, 421, 10.1038/nature24652 · DOI
  28. Sugiharto, 2008, Anion-cation permeability correlates with hydrated counterion size in glycine receptor channels, Biophys. J., 95, 4698, 10.1529/biophysj.107.125690 · DOI
  29. Barger, 2016, Near-membrane electric field calcium ion dehydration, Cell Calcium, 60, 415, 10.1016/j.ceca.2016.09.006 · DOI
  30. Rasmussen, 2019, Interaction of the Mechanosensitive Channel, MscS, with the Membrane Bilayer through Lipid Intercalation into Grooves and Pockets, J. Mol. Biol., 431, 3339, 10.1016/j.jmb.2019.05.043 · DOI
  31. Flegler, 2021, Mechanosensitive channel gating by delipidation, Proc. Natl. Acad. Sci. USA, 118, 10.1073/pnas.2107095118 · DOI
  32. Laganowsky, 2014, Membrane proteins bind lipids selectively to modulate their structure and function, Nature, 510, 172, 10.1038/nature13419 · DOI
  33. LeVine, 2016, Role of Annular Lipids in the Functional Properties of Leucine Transporter LeuT Proteomicelles, Biochemistry, 55, 850, 10.1021/acs.biochem.5b01268 · DOI
  34. Zhang, 2021, Visualization of the mechanosensitive ion channel MscS under membrane tension, Nature, 590, 509, 10.1038/s41586-021-03196-w · DOI
  35. Pliotas, 2015, The role of lipids in mechanosensation, Nat. Struct. Mol. Biol., 22, 991, 10.1038/nsmb.3120 · DOI
  36. Brohawn, 2014, Physical mechanism for gating and mechanosensitivity of the human TRAAK K+ channel, Nature, 516, 126, 10.1038/nature14013 · DOI
  37. Kalienkova, 2019, Stepwise activation mechanism of the scramblase nhTMEM16 revealed by cryo-EM, Elife, 8, 10.7554/eLife.44364 · DOI
  38. Peters, 2018, The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel, Neuron, 97, 1063, 10.1016/j.neuron.2018.01.048 · DOI
  39. Reddy, 2019, Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS, Elife, 8, 10.7554/eLife.50486 · DOI
  40. Bavi, 2016, The role of MscL amphipathic N terminus indicates a blueprint for bilayer-mediated gating of mechanosensitive channels, Nat. Commun., 7, 10.1038/ncomms11984 · DOI
  41. Rohl, 1999, Solution structure of the sodium channel inactivation gate, Biochemistry, 38, 855, 10.1021/bi9823380 · DOI
  42. Cuello, 2010, Structural mechanism of C-type inactivation in K(+) channels, Nature, 466, 203, 10.1038/nature09153 · DOI
  43. Payandeh, 2012, Crystal structure of a voltage-gated sodium channel in two potentially inactivated states, Nature, 486, 135, 10.1038/nature11077 · DOI
  44. Pau, 2017, Crystal structure of an inactivated mutant mammalian voltage-gated K(+) channel, Nat. Struct. Mol. Biol., 24, 857, 10.1038/nsmb.3457 · DOI
  45. Lolicato, 2020, K2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions, Sci. Adv., 6, 10.1126/sciadv.abc9174 · DOI
  46. Mansoor, 2016, X-ray structures define human P2X(3) receptor gating cycle and antagonist action, Nature, 538, 66, 10.1038/nature19367 · DOI
  47. Akabas, 2013, Using molecular dynamics to elucidate the structural basis for function in pLGICs, Proc. Natl. Acad. Sci. USA, 110, 16700, 10.1073/pnas.1316157110 · DOI
  48. Zheng, 2019, A hydrophobic gate in the inner pore helix is the major determinant of inactivation in mechanosensitive Piezo channels, Elife, 8, 10.7554/eLife.44003 · DOI
  49. Lewis, 2020, Inactivation Kinetics and Mechanical Gating of Piezo1 Ion Channels Depend on Subdomains within the Cap, Cell Rep., 30, 870, 10.1016/j.celrep.2019.12.040 · DOI
  50. Jiang, 2021, Structural Designs and Mechanogating Mechanisms of the Mechanosensitive Piezo Channels, Trends Biochem. Sci., 46, 472, 10.1016/j.tibs.2021.01.008 · DOI
  51. Goehring, 2014, Screening and large-scale expression of membrane proteins in mammalian cells for structural studies, Nat. Protoc., 9, 2574, 10.1038/nprot.2014.173 · DOI
  52. Rothbauer, 2008, A versatile nanotrap for biochemical and functional studies with fluorescent fusion proteins, Mol. Cell. Proteomics, 7, 282, 10.1074/mcp.M700342-MCP200 · DOI
  53. Suloway, 2005, Automated molecular microscopy: the new Leginon system, J. Struct. Biol., 151, 41, 10.1016/j.jsb.2005.03.010 · DOI
  54. Zheng, 2017, MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy, Nat. Methods, 14, 331, 10.1038/nmeth.4193 · DOI
  55. Punjani, 2017, cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination, Nat. Methods, 14, 290, 10.1038/nmeth.4169 · DOI · Paper page
  56. Li, 2020, High-Throughput Cryo-EM Enabled by User-Free Preprocessing Routines, Structure, 28, 858, 10.1016/j.str.2020.03.008 · DOI
  57. Zhang, 2016, Gctf: Real-time CTF determination and correction, J. Struct. Biol., 193, 1, 10.1016/j.jsb.2015.11.003 · DOI
  58. Scheres, 2012, RELION: implementation of a Bayesian approach to cryo-EM structure determination, J. Struct. Biol., 180, 519, 10.1016/j.jsb.2012.09.006 · DOI · Paper page
  59. Zivanov, 2020, Estimation of high-order aberrations and anisotropic magnification from cryo-EM data sets in RELION-3.1, IUCrJ, 7, 253, 10.1107/S2052252520000081 · DOI
  60. Rohou, 2015, CTFFIND4: Fast and accurate defocus estimation from electron micrographs, J. Struct. Biol., 192, 216, 10.1016/j.jsb.2015.08.008 · DOI
  61. Ramlaul, 2020, Mitigating local over-fitting during single particle reconstruction with SIDESPLITTER, J. Struct. Biol., 211, 10.1016/j.jsb.2020.107545 · DOI
  62. Ramírez-Aportela, 2020, Automatic local resolution-based sharpening of cryo-EM maps, Bioinformatics, 36, 765, 10.1093/bioinformatics/btz671 · DOI
  63. Vilas, 2018, MonoRes: Automatic and Accurate Estimation of Local Resolution for Electron Microscopy Maps, Structure, 26, 337, 10.1016/j.str.2017.12.018 · DOI
  64. de la Rosa-Trevín, 2013, Xmipp 3.0: an improved software suite for image processing in electron microscopy, J. Struct. Biol., 184, 321, 10.1016/j.jsb.2013.09.015 · DOI
  65. de la Rosa-Trevín, 2016, Scipion: A software framework toward integration, reproducibility and validation in 3D electron microscopy, J. Struct. Biol., 195, 93, 10.1016/j.jsb.2016.04.010 · DOI
  66. Sanchez-Garcia, 2021, DeepEMhancer: a deep learning solution for cryo-EM volume post-processing, Commun. Biol., 4, 874, 10.1038/s42003-021-02399-1 · DOI
  67. Waterhouse, 2018, SWISS-MODEL: homology modelling of protein structures and complexes, Nucleic Acids Res., 46, W296, 10.1093/nar/gky427 · DOI
  68. Pettersen, 2004, UCSF Chimera--a visualization system for exploratory research and analysis, J. Comput. Chem., 25, 1605, 10.1002/jcc.20084 · DOI
  69. Emsley, 2004, Coot: model-building tools for molecular graphics, Acta Crystallogr. D, 60, 2126, 10.1107/S0907444904019158 · DOI · Paper page
  70. Casañal, 2020, Current developments in Coot for macromolecular model building of Electron Cryo-microscopy and Crystallographic Data, Protein Sci., 29, 1069, 10.1002/pro.3791 · DOI
  71. Moriarty, 2009, electronic Ligand Builder and Optimization Workbench (eLBOW): a tool for ligand coordinate and restraint generation, Acta Crystallogr. D Biol. Crystallogr., 65, 1074, 10.1107/S0907444909029436 · DOI
  72. Liebschner, 2019, Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix, Acta Crystallogr. D Struct. Biol., 75, 861, 10.1107/S2059798319011471 · DOI · Paper page
  73. Afonine, 2018, Real-space refinement in PHENIX for cryo-EM and crystallography, Acta Crystallogr. D Struct. Biol., 74, 531, 10.1107/S2059798318006551 · DOI
  74. Wang, 2016, Automated structure refinement of macromolecular assemblies from cryo-EM maps using Rosetta, Elife, 5, e17219, 10.7554/eLife.17219 · DOI · Paper page
  75. Croll, 2018, ISOLDE: a physically realistic environment for model building into low-resolution electron-density maps, Acta Crystallogr. D Struct. Biol., 74, 519, 10.1107/S2059798318002425 · DOI
  76. Williams, 2018, MolProbity: More and better reference data for improved all-atom structure validation, Protein Sci., 27, 293, 10.1002/pro.3330 · DOI · Paper page
  77. Barad, 2015, EMRinger: side chain-directed model and map validation for 3D cryo-electron microscopy, Nat. Methods, 12, 943, 10.1038/nmeth.3541 · DOI · Paper page
  78. Afonine, 2018, New tools for the analysis and validation of cryo-EM maps and atomic models, Acta Crystallogr. D Struct. Biol., 74, 814, 10.1107/S2059798318009324 · DOI
  79. Klesse, 2019, CHAP: A Versatile Tool for the Structural and Functional Annotation of Ion Channel Pores, J. Mol. Biol., 431, 3353, 10.1016/j.jmb.2019.06.003 · DOI
  80. Goddard, 2018, UCSF ChimeraX: Meeting modern challenges in visualization and analysis, Protein Sci., 27, 14, 10.1002/pro.3235 · DOI · Paper page
  81. Sievers, 2011, Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega, Mol. Syst. Biol., 7, 539, 10.1038/msb.2011.75 · DOI
  82. Robert, 2014, Deciphering key features in protein structures with the new ENDscript server, Nucleic Acids Res., 42, W320, 10.1093/nar/gku316 · DOI · Paper page
  83. Hopf, 2019, The EVcouplings Python framework for coevolutionary sequence analysis, Bioinformatics, 35, 1582, 10.1093/bioinformatics/bty862 · DOI
  84. Wagih, 2017, ggseqlogo: a versatile R package for drawing sequence logos, Bioinformatics, 33, 3645, 10.1093/bioinformatics/btx469 · DOI

Metadata

Authors
Jojoa-Cruz, S., Burendei, B., Lee, W.-H., & Ward, A. B.
Affiliations
Scripps Research Institute (US)
Corresponding author
Ward, Andrew B.
ORCID
Venue
Structure
Publisher
Elsevier BV
Published
2024-02
Volume
32
Issue
2
Pages
157-167.e5
ISSN
0969-2126 (ISSN-L)
DOI
10.1016/j.str.2023.11.009
PMC
PMC10872982
OpenAlex
W4389818930
Cited by
20
References
2
Citations by year
2026: 2 · 2025: 7 · 2024: 6
FWCI
1.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Structure (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
  • National Institute of Allergy and Infectious Diseases
  • Ray Thomas Edwards Foundation
  • National Institutes of Health (P41-GM103311, R01-GM129325)
  • National Heart Lung and Blood Institute (R01 HL143297)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
mechanosensitive ion channels, Arabidopsis thaliana, transmembrane domain, conformational heterogeneity, mechanosensing, pore constriction, peptidisc

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