1932

Abstract

Cryo-electron microscopy (cryo-EM) of biological molecules in single-particle (i.e., unordered, nonaggregated) form is a new approach to the study of molecular assemblies, which are often too large and flexible to be amenable to X-ray crystallography. New insights into biological function on the molecular level are expected from cryo-EM applied to the study of such complexes “trapped” at different stages of their conformational changes and dynamical interactions. Important molecular machines involved in the fundamental processes of transcription, mRNA splicing, and translation are examples for successful applications of the new technique, combined with structural knowledge gained by conventional techniques of structure determination, such as X-ray crystallography and NMR.

Loading

Article metrics loading...

/content/journals/10.1146/annurev.biophys.31.082901.134202
2002-06-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/biophys/31/1/annurev.biophys.31.082901.134202.html?itemId=/content/journals/10.1146/annurev.biophys.31.082901.134202&mimeType=html&fmt=ahah

Literature Cited

  1. Agrawal RK, Heagle AB, Penczek P, Grassucci RA, Frank J. 1999. EF-G-dependent GTP hydrolysis induces translocation accompanied by large conformational changes in the 70S ribosome.. Nat. Struct. Biol. 6:643–47 [Google Scholar]
  2. Agrawal RK, Penczek P, Grassucci RA, Frank J. 1998. Visualization of elongation factor G on the Escherichia coli 70S ribosome: the mechanism of translocation.. Proc. Natl. Acad. Sci. USA 95:6134–38 [Google Scholar]
  3. Agrawal RK, Penczek P, Grassucci RA, Li Y, Leith A. et al. 1996. Direct visualization of A-, P-, and E-site transfer RNAs in the Escherichia coli ribosome.. Science 271:1000–2 [Google Scholar]
  4. Agrawal RK, Spahn CMT, Penczek P, Grassucci RA, Nierhaus KH, Frank J. 2000. Visualization of tRNA movements on the Escherichia coli 70S ribosome during the elongation cycle.. J. Cell Biol. 150:447–59 [Google Scholar]
  5. Alberts B. 1998. The cell as a collection of protein machines: preparing the next generation of molecular biologists.. Cell 92:291–94 [Google Scholar]
  6. Andel F, Ladurner AG, Inouye C, Tjian R, Nogales E. 1999. Three-dimensional structure of the human TFIID-IIA-IIB complex.. Science 286:2153–56 [Google Scholar]
  7. Ban N, Nissen P, Hansen J, Moore PB, Steitz TA. 2000. The complete atomic structure of the large ribosomal subunit at 2.4 Å resolution.. Science 289:905–20 [Google Scholar]
  8. Böhm J, Frangakis AS, Hergel R, Nickell S, Typke D, Baumeister W. 2000. Toward detecting and identifying macromolecules in a cellular context: template matching applied to electron tomograms.. Proc. Natl. Acad. Sci. USA 97:14245–50 [Google Scholar]
  9. Boisset N, Penczek P, Taveau JC, Frank J. 1995. Three-dimensional reconstruction in vitreous ice of Androctonus australis hemocyanin labeled with a monoclonal Fab fragment.. J. Struct. Biol. 115:16–29 [Google Scholar]
  10. Borland L, van Heel M. 1990. Classification of image data in conjugate representation spaces.. J. Opt. Soc. Am. A7:601–10 [Google Scholar]
  11. Böttcher B, Wynne SA, Crowther RA. 1997. Determination of the fold of the core protein of hepatitis B virus by electron cryomicroscopy.. Nature 386:88–91 [Google Scholar]
  12. Cheng RH, Kuhn RJ, Olson NH, Rossmann MG, Choi H-K. et al. 1995. Nucleocapsid and glycoprotein organization in an enveloped virus.. Cell 80:621–30 [Google Scholar]
  13. Chiu W, Downing KH, Dubochet J, Glaeser RM, Heide HG. et al. 1986. Cryoprotection in electron microscopy.. J. Microsc. 141:385–91 [Google Scholar]
  14. Crowther RA. 1971. Procedures for three-dimensional reconstruction of spherical viruses by Fourier synthesis from electron micrographs.. Proc. R. Soc. London. Ser. B 261:221–30 [Google Scholar]
  15. DeRosier D, Klug A. 1968. Reconstruction of 3-dimensional structures from electron micrographs.. Nature 217:130–34 [Google Scholar]
  16. DeRosier DJ. 1997. Who needs crystals anyway?. Nature 386:26–27 [Google Scholar]
  17. Dubochet J, Adrian M, Lepault J, McDowall AW. 1985. Cryo-electron microscopy of vitrified biological specimens.. Trends Biochem. Sci. 10:143–46 [Google Scholar]
  18. Dubochet J, Lepault J, Freeman R, Berriman JA, Homo JC. 1982. Electron microscopy of frozen water and aqueous solutions.. J. Microsc. 128:219–37 [Google Scholar]
  19. Frank J. 1975. Averaging of low exposure electron micrographs of non-periodic objects.. Ultramicroscopy 1:159–62 [Google Scholar]
  20. Frank J. 1996. Three-Dimensional Electron Microscopy of Macromolecular Assemblies. New York: Academic [Google Scholar]
  21. Frank J, Agrawal RK. 2000. A ratchet-like inter-subunit reorganization of the ribosome during translocation.. Nature 406:318–22 [Google Scholar]
  22. Frank J, Al-Ali L. 1975. Signal-to-noise ratio of electron micrographs obtained by cross correlation.. Nature 256:376–79 [Google Scholar]
  23. Frank J, Goldfarb W, Eisenberg D, Baker TS. 1978. Reconstruction of glutamine synthetase using computer averaging.. Ultramicroscopy 3:283–90 [Google Scholar]
  24. Frank J, Penczek P, Agrawal RK, Grassucci RA, Heagle AB. 1999. Three-dimensional cryo-electron microscopy of ribosomes.. Methods Enzymol. 317:276–91 [Google Scholar]
  25. Frank J, Penczek P, Grassucci R, Srivastava S. 1991. Three-dimensional reconstruction of the 70S Escherichia coli ribosome in ice: the distribution of ribosomal RNA.. J. Cell Biol. 115:597–605 [Google Scholar]
  26. Frank J, Verschoor A, Boublik M. 1981. Computer averaging of electron micrographs of 40S ribosomal subunits.. Science 214:1353–55 [Google Scholar]
  27. Frank J, Zhu J, Penczek P, Li Y, Srivastava S. et al. 1995. A model of protein synthesis based on cryo-electron microscopy of the E. coli ribosome.. Nature 376:441–44 [Google Scholar]
  28. Gabashvili IS, Agrawal RK, Spahn CMT, Grassucci RA, Frank J, Penczek P. 2000. Solution structure of the E. coli 70S ribosome at 11.5 Å resolution.. Cell 100:537–49 [Google Scholar]
  29. Grigorieff N. 1998. Three-dimensional structure of bovine NADH: ubiquinone oxidoreductase (complex I) at 22 Å in ice.. J. Mol. Biol. 277:1033–46 [Google Scholar]
  30. Grigorieff N. 2000. Resolution measurement in structures derived from single particles.. Acta Crystallogr. D 56:1270–77 [Google Scholar]
  31. Harauz G, Ottensmeyer FP. 1984. Direct three-dimensional reconstruction for macromolecular complexes from electron micrographs.. Ultramicroscopy 12:309–20 [Google Scholar]
  32. 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]
  33. Hoppe W, Schramm HJ, Sturm M, Hunsmann N, Gassmann J. 1976. Three-dimensional electron microscopy of individual biological objects.. I. Methods Z. Naturforsch A 31:645–55 [Google Scholar]
  34. Jones TA, Zhou JY, Cowan SW, Kjeldgaard M. 1991. Improved methods for building protein models in electron density maps and the location of errors in these models.. Acta Crystallogr. A 47:110–19 [Google Scholar]
  35. Lepault J, Booy FP, Dubochet J. 1983. Electron microscopy of frozen biological suspensions.. J. Microsc. 129(Pt 1):89–102 [Google Scholar]
  36. Malhotra A, Harvey SC. 1994. A quantitative model of the Escherichia coli 16 S RNA in the 30 S ribosomal subunit.. J. Mol. Biol. 240:308–40 [Google Scholar]
  37. Malhotra A, Penczek P, Agrawal RK, Gabashvili IS, Grassucci RA. et al. 1998. Escherichia coli 70 S ribosome at 15 Å resolution by cryo-electron microscopy: localization of fMet-tRNAfMet and fitting of L1 protein.. J. Mol. Biol. 280:103–16 [Google Scholar]
  38. Mancini EJ, Fuller SD. 2000. Supplanting crystallography or supplementing microscopy? A combined approach to the study of an enveloped virus.. Acta Crystallogr. D 56:1278–87 [Google Scholar]
  39. McEwen B, Frank J. 2001. Electron tomographic (and other approaches) for imaging molecular machines.. Curr. Opin. Neurobiol. 11:594–600 [Google Scholar]
  40. Milligan RA, Unwin PN. 1986. Location of exit channel for nascent protein in 80S ribosome.. Nature 319:693–95 [Google Scholar]
  41. Müller F, Sommer I, Baranov P, Matadeen R, Stoldt M. et al. 2000. The 3D arrangement of the 23S and 5S rRNA in the E. coli ribosomal subunit based on a cryo-electron microscopic reconstruction at 7.5 Å resolution.. J. Mol. Biol. 298:35–59 [Google Scholar]
  42. Nogales E. 2000. Recent structural insights into transcription preinitiation complexes.. J. Cell Sci. 113:4391–97 [Google Scholar]
  43. Nogales E, Grigorieff N. 2001. Molecular machines: putting the pieces together.. J. Cell Biol. 152:F1–10 [Google Scholar]
  44. Orlova EV. 2000. Structural analysis of non-crystalline macromolecules: the ribosome.. Acta Crystallogr. D 56:1253–58 [Google Scholar]
  45. Orlova EV, Dube P, Harris JR, Beckman E, Zemlin F. et al. 1997. Structure of keyhole limpet hemocyanin type 1 (KLH1) at 15 Å resolution by electron cryomicroscopy and angular reconstitution.. J. Mol. Biol. 271:417–37 [Google Scholar]
  46. Penczek PA, Grassucci RA, Frank J. 1994. The ribosome at improved resolution: new techniques for merging and orientation refinement in 3D cryo-electron microscopy of biological particles.. Ultramicroscopy 53:251–70 [Google Scholar]
  47. Penczek PA, Zhu J, Frank J. 1996. A common-lines based method for determining orientations for N > 3 particle projections simultaneously.. Ultramicroscopy 63:205–18 [Google Scholar]
  48. Radermacher M, Rao V, Grassucci R, Frank J, Timerman AP. et al. 1994. Cryoelectron microscopy and three-dimensional reconstruction of the calcium release channel/ryanodine receptor from skeletal muscle.. J. Cell Biol. 127:411–23 [Google Scholar]
  49. Radermacher M, Wagenknecht T, Verschoor A, Frank J. 1986. A new 3-D reconstruction scheme applied to the 50S ribosomal subunit of E. coli.. J. Microsc. 141:RP1–2 [Google Scholar]
  50. Radermacher M, Wagenknecht T, Verschoor A, Frank J. 1987. Three-dimensional reconstruction from a single-exposure, random conical tilt series applied to the 50S ribosomal subunit of Escherichia coli.. J. Microsc. 146:113–36 [Google Scholar]
  51. Radermacher M, Wagenknecht T, Verschoor A, Frank J. 1987. Three-dimensional structure of the large ribosomal subunit from Escherichia coli.. EMBO J. 6:1107–14 [Google Scholar]
  52. Radon J. 1917. Über die Bestimmung von Funktionen durch ihre Integralwerte längs gewisser Mannigfaltigkeiten.. Berichte über die Verhandlungen der königlich sächsischen Gesellschaft der Wissenschaften zu Leipzig Math. Phys. Klasse 69:262–77 [Google Scholar]
  53. Rayment I, Holden HM, Whittaker M, Yohn CB, Lorenz M. et al. 1993. Structure of the actin-myosin complex and its implications for muscle contraction.. Science 261:58–65 [Google Scholar]
  54. Roseman AM. 2000. Docking structures of domains into maps from cryo-electron microscopy using local correlation.. Acta Crystallogr. D 56:1332–40 [Google Scholar]
  55. Rossmann MG. 2000. Fitting atomic models into electron-microscopy maps.. Acta Crystallogr. D 56:1341–49 [Google Scholar]
  56. Rouiller I, Butel VM, Latterich M, Milligan R, Wilson-Kubalek EM. 2000. A major conformational change in p97 AAA ATPase upon ATP binding.. Mol. Cell 6:1485–90 [Google Scholar]
  57. Saibil HR. 2000. Macromolecular structure determination by cryo-electron microscopy.. Acta Crystallogr. D 56:1215–22 [Google Scholar]
  58. Saibil HR. 2000. Molecular chaperones: containers and surfaces for folding, stabilising or unfolding proteins.. Curr. Opin. Struct. Biol. 10:251–58 [Google Scholar]
  59. Saxton WO, Baumeister W. 1982. The correlation averaging of a regularly arranged bacterial envelope protein.. J. Microsc. 127:127–38 [Google Scholar]
  60. Schlünzen F, Tocilj A, Zarivach R, Harms J, Glühmann M. et al. 2000. Structure of functionally activated small ribosomal subunit at 3.3 Å resolution.. Cell 102:615–23 [Google Scholar]
  61. Schröder RR, Manstein DJ, Jahn W, Holden H, Rayment I. et al. 1993. Three-dimensional atomic model of F-actin decorated with Dictyostelium myosin S1.. Nature 364:171–74 [Google Scholar]
  62. Schultz P, Fribourg S, Poterszman A, Chipoulet M, Mallouh V. et al. 2000. Molecular architecture of human TFIIH.. Cell 102:599–607 [Google Scholar]
  63. Spahn CMT, Blaha G, Agrawal RK, Penczek P, Grassucci RA. et al. 2001. Localization of the tetracycline resistance protein Tet(O) on the ribosome and the inhibition mechanism of tetracycline.. Mol. Cell 7:1037–45 [Google Scholar]
  64. Stark H, Dube P, Lührmann R, Kastner B. 2001. Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle.. Nature 409:539–42 [Google Scholar]
  65. Stark H, Müller F, Orlova EV, Schatz M, Dube P. et al. 1995. The 70S Escherichia coli ribosome at 23 Å resolution: fitting the ribosomal RNA.. Structure 3:815–21 [Google Scholar]
  66. Stark H, Orlova EV, Rinke-Appel J, Junke N, Müller F. et al. 1997. Arrangement of tRNAs in pre- and post-translational ribosomes revealed by electron cryomicroscopy.. Cell 88:19–28 [Google Scholar]
  67. Stark H, Rodnina MV, Rinke-Appel J, Brimacombe R, Wintermeyer W, van Heel M. 1997. Visualization of elongation factor Tu on the Escherichia coli ribosome.. Nature 389:403–6 [Google Scholar]
  68. Stewart M. 1991. Transmission electron microscopy of vitrified biological macromolecular assemblies. In Electron Microscopy in Biology—A Practical Approach, ed. JR Harris 229–42 Oxford, UK: IRL
  69. Stewart PL, Fuller SD, Burnett RM. 1993. Difference imaging of adenovirus: bridging the resolution gap between X-ray crystallography and electron microscopy.. EMBO J. 12:2589–99 [Google Scholar]
  70. Deleted in proof
  71. Taylor K, Glaeser RM. 1974. Electron diffraction of frozen, hydrated protein crystals.. Science 186:1036–37 [Google Scholar]
  72. Unwin PN, Henderson R. 1975. Molecular structure determination by electron microscopy of unstained crystalline specimens.. J. Mol. Biol. 94:425–40 [Google Scholar]
  73. van Heel M. 1987. Angular reconstitution: a posteriori assignment of projection directions for 3D reconstruction.. Ultramicroscopy 21:111–24 [Google Scholar]
  74. van Heel M. 1989. Classification of very large electron microscopial image data sets.. Optik 82:114–26 [Google Scholar]
  75. van Heel M, Frank J. 1981. Use of multivariate statistics in analysing the images of biological macromolecules.. Ultramicroscopy 6:187–94 [Google Scholar]
  76. van Heel M, Harauz G. 1986. Resolution criteria for three-dimensional reconstruction.. Optik 73:119–22 [Google Scholar]
  77. van Heel M, Keegstra W, Schutter W, van Bruggen EJF. 1982. Arthropod hemocyanin structures studied by image analysis. In Life Chemistry Reports, The Structure and Function of Invertebrate Respiratory Proteins (Suppl. 1), ed. EJ Wood 69–73 London: Harwood Acad
  78. Volkmann N, Hanein D. 1999. Quantitative fitting of atomic models into observed densities derived by electron microscopy.. J. Struct. Biol 125:176–84 [Google Scholar]
  79. Volkman N, Hanein D, Ouyang G, Trybus KM, DeRosier DJ, Lowey S. 2000. Evidence for cleft closure in actomyosin upon ADP release.. Nat. Struct. Biol. 7:1147–55 [Google Scholar]
  80. Wagenknecht T, Carazo JM, Radermacher M, Frank J. 1989. Three-dimensional reconstruction of the ribosome from Escherichia coli ribosome in the range of overlap views.. Biophys. J. 55:465–77 [Google Scholar]
  81. Wagenknecht T, Grassucci R, Frank J. 1988. Electron microscopy and computer image averaging of ice-embedded large ribosomal subunits from Escherichia coli.. J. Mol. Biol. 199:137–47 [Google Scholar]
  82. Deleted in proof
  83. Wimberly BT, Brodersen DE, Clemons WM Jr, Morgan-Warren RJ, Carter AP. et al. 2000. Structure of the 30S ribosomal subunit.. Nature 407:327–39 [Google Scholar]
  84. Wriggers W, Agrawal RK, Drew DL, McCammon A, Frank J. 2000. Domain motions of EF-G bound to the 70S ribosome: insights from a hand-shaking between multi-resolution structures.. Biophys. Chem. 79:1670–78 [Google Scholar]
  85. Wriggers W, Milligan RA, McCammon JA. 1999. Situs: a package for docking crystal structures into low-resolution maps from electron microscopy.. J. Struct. Biol. 125:185–95 [Google Scholar]
  86. Wriggers W, Milligan RA, Schulten K, McCammon JA. 1998. Self-organizing neural networks bridge the biomolecular resolution gap.. J. Mol. Biol. 284:1247–54 [Google Scholar]
  87. Yonath A, Leonard KR, Wittmann HG. 1987. A tunnel in the large ribosomal subunit revealed by three-dimensional image reconstruction.. Science 236:813–16 [Google Scholar]
  88. Yusupov MM, Yusupova GZ, Baucom A, Lieberman K, Earnest TN. et al. 2001. Crystal structure of the ribosome at 5.5 Å resolution.. Science 292:883–96 [Google Scholar]
  89. Zhang X, Shaw A, Bates PA, Newman RH, Gowen B. et al. 2000. Structure of the AAA ATPase p97.. Mol. Cell 6:1473–84 [Google Scholar]
/content/journals/10.1146/annurev.biophys.31.082901.134202
Loading
/content/journals/10.1146/annurev.biophys.31.082901.134202
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error