1932

Abstract

Impressive though the achievements of single-particle cryo–electron microscopy are today, a substantial gap still remains between what is currently accomplished and what is theoretically possible. As is reviewed here, twofold or more improvements are possible as regards () the detective quantum efficiency of cameras at high resolution, () converting phase modulations to intensity modulations in the image, and () recovering the full amount of high-resolution signal in the presence of beam-induced motion of the specimen. In addition, potential for improvement is reviewed for other topics such as optimal choice of electron energy, use of aberration correctors, and quantum metrology. With the help of such improvements, it does not seem to be too much to imagine that determining the structural basis for every aspect of catalytic control, signaling, and regulation, in any type of cell of interest, could easily be accelerated fivefold or more.

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/content/journals/10.1146/annurev-biophys-070317-032828
2019-05-06
2024-06-24
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Literature Cited

  1. 1.
    Bai X-c, Fernandez IS, McMullan G, Scheres SHW 2013. Ribosome structures to near-atomic resolution from thirty thousand cryo-EM particles. eLife 2:e00461
    [Google Scholar]
  2. 2.
    Bai X-c, Yan C, Yang G, Lu P, Ma D et al. 2015. An atomic structure of human γ-secretase. Nature 525:212–17
    [Google Scholar]
  3. 3.
    Baker LA, Smith EA, Bueler SA, Rubinstein JL 2010. The resolution dependence of optimal exposures in liquid nitrogen temperature electron cryomicroscopy of catalase crystals. J. Struct. Biol. 169:431–37
    [Google Scholar]
  4. 4.
    Bammes BE, Jakana J, Schmid MF, Chiu W 2010. Radiation damage effects at four specimen temperatures from 4 to 100 K. J. Struct. Biol. 169:331–41
    [Google Scholar]
  5. 5.
    Battaglia M, Contarato D, Denes P, Doering D, Duden T et al. 2010. Characterisation of a CMOS active pixel sensor for use in the TEAM microscope. Nuclear Instrum. Methods Phys. Res. Sect. A 622:669–77
    [Google Scholar]
  6. 6.
    Boersch H 1947. Uber die Kontraste von Atomen im Electronenmikroskop. Z. Naturforsch. A 2:615–33
    [Google Scholar]
  7. 7.
    Breedlove JR, Trammell GT 1970. Molecular microscopy: fundamental limitations. Science 170:1310–13
    [Google Scholar]
  8. 8.
    Brilot AF, Chen JZ, Cheng AC, Pan JH, Harrison SC et al. 2012. Beam-induced motion of vitrified specimen on holey carbon film. J. Struct. Biol. 177:630–37
    [Google Scholar]
  9. 9.
    Campbell MG, Cheng AC, Brilot AF, Moeller A, Lyumkis D et al. 2012. Movies of ice-embedded particles enhance resolution in electron cryo-microscopy. Structure 20:1823–28
    [Google Scholar]
  10. 10.
    Cohen HA, Schmid MF, Chiu W 1984. Estimates of validity of projection approximation for 3-dimensional reconstructions at high resolution. Ultramicroscopy 14:219–26
    [Google Scholar]
  11. 11.
    Crowther RA 2016. Preface. Methods in Enzymology 579 The Resolution Revolution: Recent Advances in Cryo-EM, ed. RA Crowther xiii–xx Cambridge, MA: Academic Press
    [Google Scholar]
  12. 12.
    Crowther RA, DeRosier DJ, Klug A 1970. The reconstruction of a three-dimensional structure from projections and its application to electron microscopy. Proc. R. Soc. A 317:319–40
    [Google Scholar]
  13. 13.
    Dai XH, Zhou ZH 2018. Structure of the herpes simplex virus 1 capsid with associated tegument protein complexes. Science 360:eaa07298
    [Google Scholar]
  14. 14.
    Danev R, Baumeister W 2016. Cryo-EM single particle analysis with the Volta phase plate. eLife 5:e13046
    [Google Scholar]
  15. 15.
    Danev R, Buijsse B, Khoshouei M, Plitzko JM, Baumeister W 2014. Volta potential phase plate for in-focus phase contrast transmission electron microscopy. PNAS 111:15635–40
    [Google Scholar]
  16. 16.
    Danev R, Tegunov D, Baumeister W 2017. Using the Volta phase plate with defocus for cryo-EM single particle analysis. eLife 6:e23006
    [Google Scholar]
  17. 17.
    DeRosier DJ 2000. Correction of high-resolution data for curvature of the Ewald sphere. Ultramicroscopy 81:83–98
    [Google Scholar]
  18. 18.
    Downing KH, Glaeser RM 2008. Restoration of weak phase-contrast images recorded with a high degree of defocus: the “twin image” problem associated with CTF correction. Ultramicroscopy 108:921–28
    [Google Scholar]
  19. 19.
    Downing KH, Glaeser RM 2018. Estimating the effect of finite depth of field in single-particle cryo-EM. Ultramicroscopy 184:94–99
    [Google Scholar]
  20. 20.
    Earl LA, Falconieri V, Milne JLS, Subramaniam S 2017. Cryo-EM: beyond the microscope. Curr. Opin. Struct. Biol. 46:71–78
    [Google Scholar]
  21. 21.
    Frank J 2006. Three-Dimensional Electron Microscopy of Macromolecular Assemblies: Visualization of Biological Molecules in Their Native State New York: Oxford Univ. Press
    [Google Scholar]
  22. 22.
    Gao Y, Cao E, Julius D, Cheng Y 2016. TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action. Nature 534:347–51
    [Google Scholar]
  23. 23.
    Glaeser RM 1971. Limitations to significant information in biological electron microscopy as a result of radiation damage. J. Ultrastruct. Res. 36:466–82
    [Google Scholar]
  24. 24.
    Glaeser RM 1999. Review: electron crystallography: present excitement, a nod to the past, anticipating the future. J. Struct. Biol. 128:3–14
    [Google Scholar]
  25. 25.
    Glaeser RM 2008. Retrospective: radiation damage and its associated “Information Limitations. .” J. Struct. Biol. 163:271–76
    [Google Scholar]
  26. 26.
    Glaeser RM 2013. Invited review article: methods for imaging weak-phase objects in electron microscopy. Rev. Sci. Instrum. 84:111101
    [Google Scholar]
  27. 27.
    Glaeser RM 2013. Stroboscopic imaging of macromolecular complexes. Nat. Methods 10:475–76
    [Google Scholar]
  28. 28.
    Glaeser RM 2016. How good can cryo-EM become. ? Nat. Methods 13:28–32
    [Google Scholar]
  29. 29.
    Glaeser RM, Downing K, DeRosier D, Chiu W, Frank J 2007. Electron Crystallography of Biological Macromolecules New York: Oxford Univ. Press
    [Google Scholar]
  30. 30.
    Glaeser RM, Sassolini S, Cambie R, Jin J, Cabrini S et al. 2013. Minimizing electrostatic charging of an aperture used to produce in-focus phase contrast in the TEM. Ultramicroscopy 135:6–15
    [Google Scholar]
  31. 31.
    Glaeser RM, Taylor KA 1978. Radiation damage relative to transmission electron microscopy of biological specimens at low temperature: a review. J. Microsc. 112:127–38
    [Google Scholar]
  32. 32.
    Grob P, Bean D, Typke D, Li XM, Nogales E, Glaeser RM 2013. Ranking TEM cameras by their response to electron shot noise. Ultramicroscopy 133:1–7
    [Google Scholar]
  33. 33.
    Hayward SB, Glaeser RM 1979. Radiation damage of purple membrane at low temperature. Ultramicroscopy 4:201–10
    [Google Scholar]
  34. 34.
    Henderson R 1995. The potential and limitations of neutrons, electrons and X-rays for atomic-resolution microscopy of unstained biological molecules. Q. Rev. Biophys. 28:171–93
    [Google Scholar]
  35. 35.
    Herzik MA Jr, Wu M, Lander GC 2017. Achieving better-than-3-Å resolution by single-particle cryo-EM at 200 keV. Nat. Methods 14:1075
    [Google Scholar]
  36. 36.
    Juffmann T, Koppell SA, Klopfer BB, Ophus C, Glaeser RM, Kasevich MA 2017. Multi-pass transmission electron microscopy. Sci. Rep. 7:1699
    [Google Scholar]
  37. 37.
    Kasinath V, Faini M, Poepsel S, Reif D, Feng XA et al. 2018. Structures of human PRC2 with its cofactors AEBP2 and JARID2. Science 359:940–44
    [Google Scholar]
  38. 38.
    Khoshouei M, Radjainia M, Baumeister W, Danev R 2017. Cryo-EM structure of haemoglobin at 3.2 Å determined with the Volta phase plate. Nat. Commun. 8:16099
    [Google Scholar]
  39. 39.
    Kühlbrandt W 2014. The resolution revolution. Science 343:1443–44
    [Google Scholar]
  40. 40.
    Kuijper M, van Hoften G, Janssen B, Geurink R, De Carlo S et al. 2015. FEI's direct electron detector developments: embarking on a revolution in cryo-TEM. J. Struct. Biol. 192:179–87
    [Google Scholar]
  41. 41.
    Kuo IAM, Glaeser RM 1975. Development of methodology for low exposure, high resolution electron microscopy of biological specimens. Ultramicroscopy 1:53–66
    [Google Scholar]
  42. 42.
    Kwiat P, Weinfurter H, Herzog T, Zeilinger A, Kasevich MA 1995. Interaction-free measurement. Phys. Rev. Lett. 74:4763–66
    [Google Scholar]
  43. 43.
    Li XM, Mooney P, Zheng S, Booth CR, Braunfeld MB et al. 2013. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nat. Methods 10:584–90
    [Google Scholar]
  44. 44.
    Liu F, Zhang Z, Csanády L, Gadsby DC, Chen J 2017. Molecular structure of the human CFTR ion channel. Cell 169:85–95
    [Google Scholar]
  45. 45.
    Marko M, Leith A, Hsieh C, Danev R 2011. Retrofit implementation of Zernike phase plate imaging for cryo-TEM. J. Struct. Biol. 174:400–12
    [Google Scholar]
  46. 46.
    McMullan G, Chen S, Henderson R, Faruqi AR 2009. Detective quantum efficiency of electron area detectors in electron microscopy. Ultramicroscopy 109:1126–43
    [Google Scholar]
  47. 47.
    McMullan G, Faruqi AR, Clare D, Henderson R 2014. Comparison of optimal performance at 300 keV of three direct electron detectors for use in low dose electron microscopy. Ultramicroscopy 147:156–63
    [Google Scholar]
  48. 48.
    McMullan G, Faruqi AR, Henderson R 2016. Direct electron detectors. Methods in Enzymology, Vol. 579: Resolution Revolution: Recent Advances in Cryo-EM RA Crowther 1–17 Cambridge, MA: Academic Press
    [Google Scholar]
  49. 49.
    Meyerson JR, Rao P, Kumar J, Chittori S, Banerjee S et al. 2014. Self-assembled monolayers improve protein distribution on holey carbon cryo-EM supports. Sci. Rep. 4:7084
    [Google Scholar]
  50. 50.
    Mueller H, Jin JA, Danev R, Spence J, Padmore H, Glaeser RM 2010. Design of an electron microscope phase plate using a focused continuous-wave laser. New J. Phys. 12:073011
    [Google Scholar]
  51. 51.
    Nogales E 2016. The development of cryo-EM into a mainstream structural biology technique. Nat. Methods 13:24–27
    [Google Scholar]
  52. 52.
    Okamoto H 2012. Possible use of a Cooper-pair box for low-dose electron microscopy. Phys. Rev. A 85:043810
    [Google Scholar]
  53. 53.
    Okamoto H, Nagatani Y 2014. Entanglement-assisted electron microscopy based on a flux qubit. Appl. Phys. Lett. 104:062604
    [Google Scholar]
  54. 54.
    Plaschka C, Lin P-C, Nagai K 2017. Structure of a pre-catalytic spliceosome. Nature 546:617–21
    [Google Scholar]
  55. 55.
    Reimer L, Kohl H 2008. Transmission Electron Microscopy Physics of Image Formation New York: Springer
    [Google Scholar]
  56. 56.
    Rosenthal PB, Henderson R 2003. Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy. J. Mol. Biol. 333:721–45
    [Google Scholar]
  57. 57.
    Ruskin RS, Yu ZH, Grigorieff N 2013. Quantitative characterization of electron detectors for transmission electron microscopy. J. Struct. Biol. 184:385–93
    [Google Scholar]
  58. 58.
    Russo CJ, Henderson R 2018. Ewald sphere correction using a single side-band image processing algorithm. Ultramicroscopy 187:26–33
    [Google Scholar]
  59. 59.
    Russo CJ, Passmore LA 2014. Ultrastable gold substrates for electron cryomicroscopy. Science 346:1377–80
    [Google Scholar]
  60. 60.
    Russo CJ, Passmore LA 2016. Ultrastable gold substrates: properties of a support for high-resolution electron cryomicroscopy of biological specimens. J. Struct. Biol. 193:33–44
    [Google Scholar]
  61. 61.
    Scheres SHW 2014. Beam-induced motion correction for sub-megadalton cryo-EM particles. eLife 3:e03665
    [Google Scholar]
  62. 62.
    Scheres SHW, Gao HX, Valle M, Herman GT, Eggermont PPB et al. 2007. Disentangling conformational states of macromolecules in 3D-EM through likelihood optimization. Nat. Methods 4:27–29
    [Google Scholar]
  63. 63.
    Schilbach S, Hantsche M, Tegunov D, Dienemann C, Wigge C et al. 2017. Structures of transcription pre-initiation complex with TFIIH and Mediator. Nature 551:204–9
    [Google Scholar]
  64. 64.
    Schroder RR 2015. Advances in electron microscopy: a qualitative view of instrumentation development for macromolecular imaging and tomography. Arch. Biochem. Biophys. 581:25–38
    [Google Scholar]
  65. 65.
    Schur FKM, Obr M, Hagen WJH, Wan W, Jakobi AJ et al. 2016. An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation. Science 353:506–8
    [Google Scholar]
  66. 66.
    Spence JCH, Hawkes PW 2008. Diffract-and-destroy: Can X-ray lasers “solve” the radiation damage problem?. Ultramicroscopy 108:1502–3
    [Google Scholar]
  67. 67.
    Tan YZ, Aiyer S, Mietzsch M, Hull JA, McKenna R et al. 2018. Sub-2 Å Ewald curvature corrected single-particle cryo-EM. Nat. Commun 9:3628
    [Google Scholar]
  68. 68.
    Thomas S, Kohstall C, Kruit P, Hommelhoff P 2014. Semitransparency in interaction-free measurements. Phys. Rev. A 90:053840
    [Google Scholar]
  69. 69.
    Unwin PNT, Henderson R 1975. Molecular-structure determination by electron-microscopy of unstained crystalline specimens. J. Mol. Biol. 94:425–40
    [Google Scholar]
  70. 70.
    Vinothkumar KR, Henderson R 2016. Single particle electron cryomicroscopy: trends, issues and future perspective. Q. Rev. Biophys. 49:1–25
    [Google Scholar]
  71. 71.
    Walter A, Steltenkamp S, Schmitz S, Holik P, Pakanavicius E et al. 2015. Towards an optimum design for electrostatic phase plates. Ultramicroscopy 153:22–31
    [Google Scholar]
  72. 72.
    Wolf M, DeRosier DJ, Grigorieff N 2006. Ewald sphere correction for single-particle electron microscopy. Ultramicroscopy 106:376–82
    [Google Scholar]
  73. 73.
    Yonekura K, Braunfeld MB, Maki-Yonekura S, Agard DA 2006. Electron energy filtering significantly improves amplitude contrast of frozen-hydrated protein at 300 kV. J. Struct. Biol. 156:524–36
    [Google Scholar]
  74. 74.
    Yonekura K, Yakushi T, Atsumi T, Maki-Yonekura S, Homma M, Namba K 2006. Electron cryomicroscopic visualization of PomA/B stator units of the sodium-driven flagellar motor in liposomes. J. Mol. Biol. 357:73–81
    [Google Scholar]
  75. 75.
    Yuan SA, Wang JL, Zhu DJ, Wang N, Gao Q et al. 2018. Cryo-EM structure of a herpesvirus capsid at 3.1 angstrom. Science 360:eaao7283
    [Google Scholar]
  76. 76.
    Zapp Machalek A 2012. Chapter 1: an owner's guide to the cell. Inside the Cell Bethesda, MD: Natl. Inst. Gen. Med. Sci.
    [Google Scholar]
  77. 77.
    Zernike F 1955. How I discovered phase contrast. Science 121:345–49
    [Google Scholar]
  78. 78.
    Zhang Y, Sun BF, Feng D, Hu HL, Chu M et al. 2017. Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein. Nature 546:248–53
    [Google Scholar]
  79. 79.
    Zheng SQ, Palovcak E, Armache JP, Verba KA, Cheng YF, Agard DA 2017. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14:331–32
    [Google Scholar]
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