1932

Abstract

Early influences led me first to medical school with a view to microbiology, but I felt the lack of a deeper foundation and changed to chemistry, which in turn led me to physics and mathematics. I moved to the University of Cape Town to work on the X-ray crystallography of some small organic compounds. I developed a new method of using molecular structure factors to solve the crystal structure, which won me a research studentship to Trinity College Cambridge and the Cavendish Laboratory. There I worked on the austenite-pearlite transition in steel. This is governed by the dissipation of latent heat, and I ended up numerically solving partial differential equations. I used the idea of nucleation and growth during the phase change, which had its echo when I later tackled the assembly of (TMV) from its constituent RNA and protein subunits.

I wanted to move on to X-ray structure analysis of large biological molecules and obtained a Nuffield Fellowship to work in J.D. Bernal's department at Birkbeck College, London. There, I met Rosalind Franklin, who had taken up the study of TMV. I was able to interpret some of Franklin's beautiful X-ray diffraction patterns of the virus particle. From then on, my fate was sealed.

After Franklin's untimely death in 1958, I moved in 1962 to the newly built MRC Laboratory of Molecular Biology in Cambridge, which, under Max Perutz, housed the original MRC unit from the Cavendish Laboratory. I was thus privileged to join the Laboratory at an early stage in its expansion and consequently able to take advantage of, and to help build up, its then unique environment of intellectual and technological sophistication. There I have remained ever since.

Loading

Article metrics loading...

/content/journals/10.1146/annurev.biochem.79.091407.093947
2010-07-07
2024-04-13
Loading full text...

Full text loading...

/deliver/fulltext/biochem/79/1/annurev.biochem.79.091407.093947.html?itemId=/content/journals/10.1146/annurev.biochem.79.091407.093947&mimeType=html&fmt=ahah

Literature Cited

  1. Fraenkel-Conrat H, Williams RC. 1.  1955. Reconstitution of active Tobacco mosaic virus from its inactive protein and nucleic acid components. Proc. Natl. Acad. Sci. USA 41:690–98 [Google Scholar]
  2. Fraenkel-Conrat H, Singer B. 2.  1959. Reconstitution of Tobacco mosaic virus. III. Improved methods and the use of mixed nucleic acids. Biochim. Biophys. Acta 33:359–70 [Google Scholar]
  3. Matthews REF. 3.  1966. Reconstitution of Turnip yellow mosaic virus RNA with TMV protein subunits. Virology 30:82–96 [Google Scholar]
  4. Stubbs G, Warren S, Holmes K. 4.  1977. Structure of RNA and RNA binding site in Tobacco mosaic virus from 4-A map calculated from X-ray fibre diagrams. Nature 267:216–21 [Google Scholar]
  5. Holmes KCJ. 5.  1979. Protein-RNA interactions during TMV assembly. J. Supramol. Struct. 12:305–20 [Google Scholar]
  6. Schramm G, Zillig WZ. 6.  1955. Überdie Struktur des Tabakmosaikvirus IV. Die Reggregation des nucleinsäuve Freien. Protein Z. Naturforschung Ser. B 10:493–98 [Google Scholar]
  7. Caspar DLD. 7.  1963. Assembly and stability of the Tobacco mosaic virus particle. Adv. Protein Chem 18:37–121 [Google Scholar]
  8. Finch JT, Leberman R, Chang Y-S, Klug A. 8.  1966. Rotational symmetry of the two turn disk aggregate of Tobacco mosaic virus protein. Nature 212:349–50 [Google Scholar]
  9. Bricogne G. 9.  1976. Methods and programs for direct-space exploitation of geometric redundancies. Acta Crystallogr. Sect. A 32:832–47 [Google Scholar]
  10. Bloomer AC, Champness JN, Bricogne G, Staden R, Klug A. 10.  1978. Protein disk of Tobacco mosaic virus at 2.8 angstrom resolution showing the interactions within and between subunits. Nature 276:362–68 [Google Scholar]
  11. Lauffer MA, Stevens CL. 11.  1968. Structure of the Tobacco mosaic virus particle; polymerization of Tobacco mosaic virus protein. Adv. Virus Res. 13:1–63 [Google Scholar]
  12. Durham AC, Finch JT, Klug A. 12.  1971. States of aggregation of Tobacco mosaic virus protein. Nat. New Biol. 299:37–42 [Google Scholar]
  13. Durham AC, Klug A. 13.  1971. Polymerization of Tobacco mosaic virus protein and its control. Nat. New Biol. 299:42–46 [Google Scholar]
  14. Klug A, Durham ACH. 14.  1971. The disk of TMV protein and its relations to the helical and other modes of aggregation. Cold Spring Harb. Symp. Quant. Biol. 36:449–60 [Google Scholar]
  15. Butler PJG, Klug A. 15.  1971. Assembly of the particle of Tobacco mosaic virus from RNA and disks of protein. Nat. New Biol. 229:47–50 [Google Scholar]
  16. Fukuda M, Ohno T, Okada Y, Otsuki Y, Takebe I. 16.  1978. Kinetics of biphasic reconstitution of Tobacco mosaic virus in vitro. Proc. Natl. Acad. Sci. USA 75:1727–30 [Google Scholar]
  17. Butler PJG, Lomonossoff GP. 17.  1980. RNA-protein interactions in the assembly of Tobacco mosaic virus. Biophys. J. 32:295–312 [Google Scholar]
  18. Zimmern D, Butler PJG. 18.  1977. The isolation of Tobacco mosaic virus RNA fragments containing the origin for viral assembly. Cell 11:455–62 [Google Scholar]
  19. Zimmern D. 19.  1977. The nucleotide sequence at the origin for assembly on Tobacco mosaic virus RNA. Cell 11:463–82 [Google Scholar]
  20. Zimmern D, Wilson TMA. 20.  1976. Location of the origin for viral reassembly on Tobacco mosaic virus RNA and its relation to stable fragment. FEBS Lett. 71:294–98 [Google Scholar]
  21. Champness JN, Bloomer AC, Bricogne G, Butler PJG, Klug A. 21.  1976. The structure of the protein disk of Tobacco mosaic virus to 5 angstrom resolution. Nature 259:20–24 [Google Scholar]
  22. Butler PJG, Bloomer AC, Bricogne G, Champness JN, Graham J. 22.  et al. 1976. Tobacco mosaic virus assembly-specificity and the transition in protein structure during RNA packaging. Structure-Function Relationships of Proteins, 3rd. John Innes Symp., ed. R Markham, RW Home 101–10 Amsterdam: North-Holland/Elsevier [Google Scholar]
  23. Klug A. 23.  1979. The assembly of Tobacco mosaic virus: structure and specificity. Harvey Lect. 74:141–72 [Google Scholar]
  24. Crowther RA, Klug A. 24.  1975. Structural analysis of macromolecular assemblies by image reconstruction from electron micrographs. Annu. Rev. Biochem. 44:161–82 [Google Scholar]
  25. Lebeurier G, Nicolaieff A, Richards KE. 25.  1977. Inside-out model for self-assembly of Tobacco mosaic virus. Proc. Natl. Acad. Sci. USA 74:149–53 [Google Scholar]
  26. Butler PJG, Finch JT, Zimmern D. 26.  1977. Configuration of Tobacco mosaic virus RNA during virus assembly. Nature 265:217–19 [Google Scholar]
  27. Caspar DLD, Klug A. 27.  1962. Physical principles in the construction of regular viruses. Cold Spring Harb. Symp. Quant. Biol. 27:1–24 [Google Scholar]
  28. Klug A. 28.  1979. Image analysis and reconstruction in the electron microscopy of biological macromolecules.. Chem. Scr. 14:245–56 [Google Scholar]
  29. Brenner S, Horne RW. 29.  1959. A negative staining method for high resolution electron microscopy of viruses. Biochim. Biphys. Acta 34:103–10 [Google Scholar]
  30. Klug A, Finch JT. 30.  1965. Structure of viruses of the papilloma-polyoma type I. human wart virus. J. Mol. Biol. 11:403–23 [Google Scholar]
  31. Klug A, Finch JT. 31.  1968. Structure of viruses of the papilloma-polyoma type IV. Analysis of tilting experiments in the electron microscope. Appendix: Symmetry relations between superposition patterns along different axes of view. J. Mol. Biol. 31:1–12 [Google Scholar]
  32. Klug A, Berger JE. 32.  1964. An optical method for the analysis of periodicities in electron micrographs and some observations on the mechanism of negative staining. J. Mol. Biol. 10:565–69 [Google Scholar]
  33. Klug A, DeRosier DJ. 33.  1966. Optical filtering of electron micrographs: reconstruction of one-sided images. Nature 212:29–32 [Google Scholar]
  34. DeRosier DJ, Klug A. 34.  1972. Structure of the tubular variants of the head of bacteriophage T4 (polyheads). I. Arrangement of subunits in some classes of polyheads. J. Mol. Biol. 65:469–88 [Google Scholar]
  35. DeRosier DJ, Klug A. 35.  1968. Reconstruction of three dimensional structure from electron micrographs. Nature 217:130–34 [Google Scholar]
  36. Crowther RA, DeRosier DJ, Klug A. 36.  1970. The reconstruction of a three-dimensional structure from projections and its application to electron microscopy. Proc. R. Soc. Lond. Ser. A 317:319–40 [Google Scholar]
  37. Crowther RA, Amos LA, Finch JT, DeRosier DJ, Klug A. 37.  1970. Three-dimensional reconstuctions of spherical viruses by Fourier synthesis from electron micrographs. Nature 226:421–25 [Google Scholar]
  38. Crowther RA, Amos LA. 38.  1971. Three-dimensional image reconstructions of some small spherical viruses. Cold Spring Harb. Symp. Quant. Biol. 36:489–94 [Google Scholar]
  39. Unwin PNT. 39.  1974. Electron microscopy of the stacked disk aggregate of Tobacco mosaic virus protein. I. Three-dimensional image reconstruction. J. Mol. Biol. 87:657–70 [Google Scholar]
  40. Taylor KA, Glaeser RM. 40.  1976. Electron microscopy of frozen hydrated biological specimens. J. Ultrastruct. Res. 55:448–56 [Google Scholar]
  41. Unwin PNT, Henderson R. 41.  1975. Molecular structure determination by electron microscopy of unstained crystalline specimens. J. Mol. Biol. 94:425–40 [Google Scholar]
  42. Henderson R, Unwin PNT. 42.  1975. Three-dimensional model of purple membrane obtained by electron microscopy. Nature 257:28–32 [Google Scholar]
  43. Unwin PNT. 43.  1972. Electron microscopy of biological specimens by means of an electrostatic phase plate. Proc. R. Soc. Lond. Ser. A 329:327–59 [Google Scholar]
  44. Erickson HP, Klug A. 44.  1970. The fourier transform of an electron micrograph: effects of defocussing and aberrations and implications for the use of underfocus contrast enhancement. Ber. Bunsen-Ges. Phys. Chem. 74:1129–37 [Google Scholar]
  45. Kornberg RD. 45.  1974. Chromatin structure: a repeating unit of histones and DNA. Science 184:868–71 [Google Scholar]
  46. Kornberg RD. 46.  1977. Structure of chromatin. Annu. Rev. Biochem. 46:931–54 [Google Scholar]
  47. Kornberg RD, Klug A. 47.  1981. The nucleosome. Sci. Am. 244:52–64 [Google Scholar]
  48. Wilkins MHF, Zubay G, Wilson HR. 48.  1959. X-ray diffraction studies of the molecular structure of nucleohistone and chromosomes. J. Mol. Biol. 1:179–85 [Google Scholar]
  49. Luzzati V, Nicolaieff A. 49.  1959. Etude par diffusion des rayons X aux petits angles des gels d'acide désoxyribonucléique et de nucléoprotéines. J. Mol. Biol. 1:127–33 [Google Scholar]
  50. Hewish DR, Burgoyne IA. 50.  1973. The digestion of chromatin DNA at regularly spaced sites by a nuclear deoxyribonuclease. Biochem. Biophys. Res. Commun. 52:504–10 [Google Scholar]
  51. Noll M. 51.  1974. Subunit structure of chromatin. Nature 251:249–51 [Google Scholar]
  52. Kornberg RD, Thomas JO. 52.  1974. Chromatin structure: oligmers of the histone. Science 184:865–68 [Google Scholar]
  53. Noll M, Kornberg RD. 53.  1977. Action of micrococcal nuclease on chromatin and the location of histone H1. J. Mol. Biol. 109:393–404 [Google Scholar]
  54. Finch JT, Lutter LC, Rhodes D, Brown RS, Rushton B. 54.  et al. 1977. Structure of nucleosome core particles of chromatin. Nature 269:29–36 [Google Scholar]
  55. Finch JT, Klug A. 55.  1978. X-ray and electron microscope analysis of crystals of nucleosome cores. Cold Spring Harb. Symp. Quant. Biol. 42:1–15 [Google Scholar]
  56. Lutter LC. 56.  1978. Kinetic analysis of deoxyribonuclease I cleavages in the nucleosome core: evidence for a DNA superhelix. J. Mol. Biol. 124:391–420 [Google Scholar]
  57. Finch JT, Brown RS, Rhodes D, Richmond T, Rushton B. 57.  et al. 1981. X-ray diffraction study of a new crystal form of the nucleosome core showing higher resolution. J. Mol. Biol. 145:757–69 [Google Scholar]
  58. Finch JT, Lewit-Bentley A, Bentley GA, Roth M, Timmins PA. 58.  1980. Neutron diffraction from crystals of nucleosome core partcles. Philos. Trans. R. Soc. Lond. B 290:635–38 [Google Scholar]
  59. Thomas JO, Kornberg RD. 59.  1975. An octamer of histones in chromatin and free in solution. Proc. Natl. Acad. Sci. USA 72:2626–30 [Google Scholar]
  60. Klug A, Rhodes D, Smith J, Finch JT, Thomas JO. 60.  1980. A low resolution structure of the histone core of the nucleosome. Nature 287:509–16 [Google Scholar]
  61. Mirzabekov AD, Shick VV, Belyavsky AV, Bavykin SG. 61.  1978. Primary organization of nucleosome core particle of chromatin: sequence of histone arrangement along DNA. Proc. Natl. Acad. Sci. USA 75:4184–88 [Google Scholar]
  62. Camerini-Otero RD, Felsenfeld G. 62.  1977. Supercoiling energy and nucleosome formation: the role of the arginine-rich histone kernel. Nucleic Acids Res. 4:1159–81 [Google Scholar]
  63. Thomas JO, Kornberg RD. 63.  1975. Cleavable cross-links in the analysis of histone-histone associations. FEBS Lett. 58:353–58 [Google Scholar]
  64. Richmond TJ, Finch JT, Rushton D, Rhodes D, Klug A. 64.  1984. Structure of the nucleosome core particle at 7 angstrom resolution. Nature 311:532–37 [Google Scholar]
  65. Luger K, Mäder AW, Richmond RK, Sargent OF, Richmond TJ. 65.  1997. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389:251–60 [Google Scholar]
  66. Finch JT, Klug A. 66.  1976. Solenoidal model for superstructure in chromatin. Proc. Natl. Acad. Sci. USA 73:1897–901 [Google Scholar]
  67. Sperling L, Klug A. 67.  1977. X-ray studies on “native” chromatin. J. Mol. Biol. 112:253–63 [Google Scholar]
  68. Simpson RT. 68.  1978. Structure of the chromatosome, a chromatin particle containing 160 base pairs of DNA and all the histones. Biochemistry 17:5524–31 [Google Scholar]
  69. Thoma F, Koller T, Klug A. 69.  1979. Involvement of histone H1 in the organization of the nucleosome and of the salt-dependent superstructures of chromatin. J. Cell Biol. 83:403–27 [Google Scholar]
  70. Robinson PJ, Fairall L, Huynh VA, Rhodes D. 70.  2006. EM measurements define the dimensions of the “30-nm” chromatin fiber: evidence for a compact, interdigitated structure. Proc. Natl. Acad. Sci. USA 103:6506–11 [Google Scholar]
  71. Worcel A, Han S, Wong ML. 71.  1978. Assembly of newly replicated chromatin. Cell 15:969–77 [Google Scholar]
  72. Senshu T, Fukuda M, Ohashi M. 72.  1978. Preferential association of newly synthesized H3 and H4 histones with newly replicated DNA. J. Biochem. 84:985–88 [Google Scholar]
  73. Cremisi C, Yaniv M. 73.  1980. Sequential assembly of newly synthesized histones on replication SV40 DNA. Biochem. Biophys. Res. Commun. 92:1117–23 [Google Scholar]
  74. Klug A, Caspar DLD. 74.  1960. The structure of small viruses. Adv. Virus Res. 7:225–325 [Google Scholar]
  75. Crowther RC, Amos LA. 75.  1971. Harmonic analysis of electron microscope images with rotational symmetry. J. Mol. Biol. 60:123–30 [Google Scholar]
  76. Klug A. 76.  2010. The discovery of zinc fingers and their applications in gene regulation and genome manipulation. Annu. Rev. Biochem. 79: 213–31 [Google Scholar]
/content/journals/10.1146/annurev.biochem.79.091407.093947
Loading
/content/journals/10.1146/annurev.biochem.79.091407.093947
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