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Cited by 649Ion Channels and ReceptorsErythrocyte Function and PathophysiologyIon channel regulation and function

Structure of the mechanically activated ion channel Piezo1

Open access
Saotome, Kei, Murthy, Swetha E., Kefauver, Jennifer M., Whitwam, Tess, Patapoutian, Ardem, Ward, Andrew B.·2018·Nature
DOI 10.1038/nature25453PMC PMC6010196
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Abstract

Piezo1 and Piezo2 are mechanically activated ion channels that mediate touch perception, proprioception and vascular development. Piezo proteins are distinct from other ion channels and their structure remains poorly defined, which impedes detailed study of their gating and ion permeation properties. Here we report a high-resolution cryo-electron microscopy structure of the mouse Piezo1 trimer. The detergent-solubilized complex adopts a three-bladed propeller shape with a curved transmembrane region containing at least 26 transmembrane helices per protomer. The flexible propeller blades can adopt distinct conformations, and consist of a series of four-transmembrane helical bundles that we term Piezo repeats. Carboxy-terminal domains line the central ion pore, and the channel is closed by constrictions in the cytosol. A kinked helical beam and anchor domain link the Piezo repeats to the pore, and are poised to control gating allosterically. The structure provides a foundation to dissect further how Piezo channels are regulated by mechanical force.

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  • The peripheral regions of Piezo, comprising the three blades, are responsible for sensing mechanical force.

    “Piezo is assembled into a trimeric propeller-like ion channel with three blades: the central region of this channel is crucial for ion permeation, while the peripheral regions, comprising the three blades, are responsible for sensing mechanical force.23,24,25,26,27”

    From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [25]

    The ‘Flexible blades’ section describes peripheral movement and suggests that membrane tension-induced changes there may be transmitted to the central gating machinery. The ‘Concluding remarks’ frame this mechanism as speculation and also implicate the central cap, so the paper does not establish that the three blades are responsible for sensing mechanical force. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Structural insights from cryo-EM studies provide a foundation for rational drug design.

    “Structural insights from cryo-EM studies provide a foundation for rational drug design, aiming to optimize affinity and specificity.25”

    From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [25]

    The Introduction’s “Gating machinery and lipid pocket” section identifies a ligand-binding pocket in the cryo-EM structure and suggests it may be a target for compounds that modulate Piezo function. That supports the potential use of structural insights in compound design, but the paper does not address rational optimization of drug affinity or specificity. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The central region of the Piezo channel is crucial for ion permeation.

    “Piezo is assembled into a trimeric propeller-like ion channel with three blades: the central region of this channel is crucial for ion permeation, while the peripheral regions, comprising the three blades, are responsible for sensing mechanical force.23,24,25,26,27”

    From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [25]

  • Piezo is assembled into a trimeric propeller-like ion channel with three blades.

    “Piezo is assembled into a trimeric propeller-like ion channel with three blades: the central region of this channel is crucial for ion permeation, while the peripheral regions, comprising the three blades, are responsible for sensing mechanical force.23,24,25,26,27”

    From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [25]

  • Previous studies confirmed the expression of Piezo1 in hepatocytes and AML12 cells.

    “Previous studies have confirmed the expression of Piezo1 in hepatocytes and AML12 cells.25,26,27,39,40,47”

    From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [25]

    The Methods (Cell culture and transfections; Sample Preparation, pages unavailable) describe Piezo1 experiments in HEK293T and HEK293F cells, not hepatocytes or AML12 cells. Searches for “hepatocytes AML12” and “liver hepatocyte hepatic cells Piezo1 expression” found no passage in our copy addressing expression in either claimed cell type. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 49

  1. [1]Ranade SS Syeda R Patapoutian A Mechanically Activated Ion Channels Neuron 87 1162 79 2015 26402601 PMC4582600
  2. [2]Coste B Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels Science 330 55 60 2010 20813920 PMC3062430
  3. [3]Coste B Piezo proteins are pore-forming subunits of mechanically activated channels Nature 483 176 81 2012 22343900 PMC3297710
  4. [4]Ranade SS Piezo2 is the major transducer of mechanical forces for touch sensation in mice Nature 516 121 U330 2014 25471886 PMC4380172
  5. [5]Woo SH Piezo2 is the principal mechanotransduction channel for proprioception Nature Neuroscience 18 1756 1762 2015 26551544 PMC4661126
  6. [6]Kim SE Coste B Chadha A Cook B Patapoutian A The role of Drosophila Piezo in mechanical nociception Nature 483 209 212 2012 22343891 PMC3297676
  7. [7]Li J Piezo1 integration of vascular architecture with physiological force Nature 515 279 282 2014 25119035 PMC4230887
  8. [8]Nonomura K Piezo2 senses airway stretch and mediates lung inflation-induced apnoea Nature 541 176-+ 2017 28002412 PMC5267560
  9. [9]Zarychanski R Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis Blood 120 1908 15 2012 22529292 PMC3448561
  10. [10]Albuisson J Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels (vol 4, pg 1884, 2013) Nature Communications 4 2013 PMC3674779 23695678
  11. [11]Andolfo I Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1 Blood 121 3925 3935 2013 23479567
  12. [12]Bae C Gnanasambandam R Nicolai C Sachs F Gottlieb PA Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1 Proc Natl Acad Sci U S A 110 E1162 8 2013 23487776 PMC3606986
  13. [13]Coste B Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis Proceedings of the National Academy of Sciences of the United States of America 110 4667 4672 2013 23487782 PMC3607045
  14. [14]Lukacs V Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia Nat Commun 6 8329 2015 26387913 PMC4578306
  15. [15]Chesler AT The Role of PIEZO2 in Human Mechanosensation New England Journal of Medicine 375 1355 1364 2016 27653382 PMC5911918
  16. [16]Mahmud AA Loss of the proprioception and touch sensation channel PIEZO2 in siblings with a progressive form of contractures Clinical Genetics 91 470 475 2017 27607563
  17. [17]Haliloglu G Recessive PIEZO2 stop mutation causes distal arthrogryposis with distal muscle weakness, scoliosis and proprioception defects Journal of Human Genetics 62 497 501 2017 27974811
  18. [18]Syeda R Piezo1 Channels Are Inherently Mechanosensitive Cell Rep 17 1739 1746 2016 27829145 PMC5129625
  19. [19]Lewis AH Grandl J Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension Elife 4 2015 PMC4718726 26646186
  20. [21]Kamajaya A Kaiser JT Lee J Reid M Rees DC The structure of a conserved piezo channel domain reveals a topologically distinct beta sandwich fold Structure 22 1520 7 2014 25242456 PMC4192063
  21. [22]Ge J Architecture of the mammalian mechanosensitive Piezo1 channel Nature 527 64 9 2015 26390154
  22. [23]Brohawn SG Campbell EB MacKinnon R Physical mechanism for gating and mechanosensitivity of the human TRAAK K+ channel Nature 516 126 30 2014 25471887 PMC4682367
  23. [24]Pliotas C The role of lipids in mechanosensation Nature Structural & Molecular Biology 22 991 998 2015 PMC4675090 26551077
  24. [25]Phillips R Ursell T Wiggins P Sens P Emerging roles for lipids in shaping membrane-protein function Nature 459 379 385 2009 19458714 PMC3169427
  25. [26]Jasti J Furukawa H Gonzales EB Gouaux E Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH Nature 449 316 23 2007 17882215
  26. [27]Kawate T Michel JC Birdsong WT Gouaux E Crystal structure of the ATP-gated P2X(4) ion channel in the closed state Nature 460 592 8 2009 19641588 PMC2720809
  27. [28]Zhao Q Ion Permeation and Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels Neuron 89 1248 63 2016 26924440
  28. [29]Long SB Campbell EB Mackinnon R Crystal structure of a mammalian voltage-dependent Shaker family K+ channel Science 309 897 903 2005 16002581
  29. [30]Liao M Cao E Julius D Cheng Y Structure of the TRPV1 ion channel determined by electron cryo-microscopy Nature 504 107 12 2013 24305160 PMC4078027
  30. [31]Drin G Antonny B Amphipathic helices and membrane curvature FEBS Lett 584 1840 7 2010 19837069
  31. [32]Bavi N The role of MscL amphipathic N terminus indicates a blueprint for bilayer-mediated gating of mechanosensitive channels Nat Commun 7 11984 2016 27329693 PMC4917966
  32. [33]Mansoor SE X-ray structures define human P2X(3) receptor gating cycle and antagonist action Nature 538 66 71 2016 27626375 PMC5161641
  33. [34]Coste B Piezo1 ion channel pore properties are dictated by C-terminal region Nature Communications 6 2015 PMC4445471 26008989
  34. [35]Wu J Lewis AH Grandl J Touch, Tension, and Transduction - The Function and Regulation of Piezo Ion Channels Trends Biochem Sci 42 57 71 2017 27743844 PMC5407468
  35. [36]Glogowska E Novel mechanisms of PIEZO1 dysfunction in hereditary xerocytosis Blood 2017 PMC5649553 28716860
  36. [37]Wu J Goyal R Grandl J Localized force application reveals mechanically sensitive domains of Piezo1 Nat Commun 7 12939 2016 27694883 PMC5063965
  37. [38]Ursell T Kondev J Reeves D Wiggins P Phillips R The Role of Lipid Bilayer Mechanics in Mechanosensation Mechanosensitive Ion Channels 1 Kamkin A Kiseleva I 37 70 Springer 2008
  38. [39]Suloway C Automated molecular microscopy: the new Leginon system J Struct Biol 151 41 60 2005 15890530
  39. [40]Zheng SQ MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy Nat Methods 14 331 332 2017 28250466 PMC5494038
  40. [41]Zhang K Gctf: Real-time CTF determination and correction J Struct Biol 193 1 12 2016 26592709 PMC4711343
  41. [42]Scheres SH RELION: implementation of a Bayesian approach to cryo-EM structure determination J Struct Biol 180 519 30 2012 23000701 PMC3690530
  42. [43]Berndsen Z Bowman C Jang H Ward AB EMHP: An accurate automated hole masking algorithm for single-particle cryo-EM image processing Bioinformatics 2017 PMC5860320 28961740
  43. [44]Bartesaghi A Matthies D Banerjee S Merk A Subramaniam S Structure of beta-galactosidase at 3.2-angstrom resolution obtained by cryo-electron microscopy Proceedings of the National Academy of Sciences of the United States of America 111 11709 11714 2014 25071206 PMC4136629
  44. [45]Emsley P Lohkamp B Scott WG Cowtan K Features and development of Coot Acta Crystallogr D Biol Crystallogr 66 486 501 2010 20383002 PMC2852313
  45. [46]Adams PD PHENIX: a comprehensive Python-based system for macromolecular structure solution Acta Crystallographica Section D-Biological Crystallography 66 213 221 2010 PMC2815670 20124702
  46. [47]Chen VB MolProbity: all-atom structure validation for macromolecular crystallography Acta Crystallographica Section D-Biological Crystallography 66 12 21 2010 PMC2803126 20057044
  47. [48]Barad BA EMRinger: side chain directed model and map validation for 3D cryo-electron microscopy Nature Methods 12 943 946 2015 26280328 PMC4589481
  48. [49]Unni S Web Servers and Services for Electrostatics Calculations with APBS and PDB2PQR Journal of Computational Chemistry 32 1488 1491 2011 21425296 PMC3062090
  49. [51]Pettersen EF UCSF Chimera--a visualization system for exploratory research and analysis J Comput Chem 25 1605 12 2004 15264254

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Authors
Saotome, K., Murthy, S. E., Kefauver, J. M., Whitwam, T., Patapoutian, A., & Ward, A. B.
Affiliations
Scripps Research Institute (US)
Corresponding author
  • Patapoutian, Ardem
  • Ward, Andrew B.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2017-12-20
Volume
554
Issue
7693
Pages
481-486
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature25453
PMC
PMC6010196
OpenAlex
W2779962245
Cited by
649
References
1
Citations by year
2026: 92 · 2025: 99 · 2024: 63 · 2023: 67 · 2022: 99 · 2021: 81 · 2020: 46 · 2019: 66 · 2018: 36
FWCI
25.49
Type
journal article
Language
en
Update notices
correction (2022-07-04)
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health (1-S10OD0211634, 1s10od021634-01)
  • National Institute of Neurological Disorders and Stroke (R01NS083174)
  • National Institute of Dental and Craniofacial Research (R01DE022358)
Topics
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
Piezo1, Piezo2, mechanosensitive ion channels, mechanotransduction, channel structure, three-bladed propeller, transmembrane helices, allosteric gating, membrane tension, tactile perception, proprioception
MeSH terms
Protein Domains, Animals, Binding Sites, Ion Channels, Lipids, Models, Molecular, Mutation, Solubility, Ion Channel Gating, Pliability, Cryoelectron Microscopy, Mice

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