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The march of structural biology

Nature Reviews Molecular Cell Biology volume 3, pages 377–381 (2002)Cite this article

Abstract

One hundred years ago, we knew very little about biological macromolecules and had no tools available to study their structure. Structural biology is now a mature science. New structures are being solved at an ever-increasing rate and there are important new initiatives to determine all the protein folds that are used by biological systems (structural genomics). This article traces some of the key developments in the field.

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Figure 1: Max Perutz (1914–2002) and John Kendrew (1917–1999).
Figure 2: Balsa-wood model of bacteriorhodopsin.
Figure 3: A figure from the first paper to describe solution-structure determination using nuclear magnetic resonance.

References

  1. Bracegirdle, B. Microscopy and comprehension: the development of understanding of the nature of the cell. Trends Biochem. Sci. 14, 464–468 (1989).

    Article  CAS  Google Scholar 

  2. Perutz, M. Early days of protein crystallography. Methods Enzymol. 114, 3–19 (1985).

    Article  CAS  Google Scholar 

  3. Rossmann, M. G. The beginnings of structural biology. Protein Sci. 3, 1731–1733 (1994).

    Article  CAS  Google Scholar 

  4. Kendrew, J. C. et al. A three-dimensional model of the myoglobin molecule obtained by X-ray analysis. Nature 181, 662–666 (1958).

    Article  CAS  Google Scholar 

  5. Bragg, L. A discussion on the structure and function of lysozyme. Proc. Roy. Soc. Ser. B 167, 349 (1967).

    Google Scholar 

  6. Rosenbaum, G. et al. Synchrotron radiation as a source for X-ray diffraction. Nature 230, 434–437 (1971).

    Article  CAS  Google Scholar 

  7. Hendrickson, W. A. Synchrotron crystallography. Trends Biochem. Sci. 25, 637–643 (2000).

    Article  CAS  Google Scholar 

  8. Ramakrishnan, V. & Moore, P. B. Atomic structures at last: the ribosome in 2000. Curr. Opin. Struct. Biol. 11, 144–154 (2001).

    Article  CAS  Google Scholar 

  9. Schoenborn, B. P. Neutron diffraction analysis of myoglobin. Nature 224, 143–146 (1969).

    Article  CAS  Google Scholar 

  10. Kossiakoff, A. A. The application of neutron crystallography to the study of dynamic and hydration properties of proteins. Annu. Rev. Biochem. 54, 1195–1227 (1985).

    Article  CAS  Google Scholar 

  11. Brenner, S. & Horne, R. W. A negative staining method for high-resolution electron microscopy of viruses. Biochim. Biophys. Acta 34, 103–110 (1959).

    Article  CAS  Google Scholar 

  12. de Rosier, D. J. & Klug, A. Reconstruction of three-dimensional structures from electron micrographs. Nature 217, 130–134 (1968).

    Article  CAS  Google Scholar 

  13. Henderson, R. & Unwin, P. N. T. Three-dimensional model of purple membrane obtained by electron microscopy. Nature 257, 28–32 (1975).

    Article  CAS  Google Scholar 

  14. Henderson, R. et al. Model for the structure of bacteriorhodopsin based on high-resolution electron cryomicroscopy. J. Mol. Biol. 213, 899–929 (1990).

    Article  CAS  Google Scholar 

  15. Stahlberg, H. et al. Two-dimensional crystals: a powerful approach to assess structure, function and dynamics of membrane proteins. FEBS Lett. 504, 166–172 (2001).

    Article  CAS  Google Scholar 

  16. Frank, J. et al. A model of protein synthesis based on cryo-electron microscopy of the E. coli ribosome. Nature 376, 441–444 (1995).

    Article  CAS  Google Scholar 

  17. Mueller, F. et al. The 3D arrangement of the 23S and 5S rRNA in the E. coli 50S ribosome subunit based on a cryo-EM reconstruction at 7.5Å resolution. J. Mol. Biol. 298, 35–59 (2000).

    Article  CAS  Google Scholar 

  18. Saibil, H. R. Conformational changes studied by cryo-EM microscopy. Nature Struct. Biol. 7, 711–714 (2000).

    Article  CAS  Google Scholar 

  19. Bloch, F., Hansen, W. W. & Packard, M. Nuclear induction. Phys. Rev. 69, 127 (1946).

    Article  Google Scholar 

  20. Purcell, E. M., Torrey, H. C. & Pound, R. V. Resonance absorption by nuclear magnetic moments in a solid. Phys. Rev. 69, 37 (1946).

    Article  CAS  Google Scholar 

  21. Saunders, M., Wishnia, A. & Kirkwood, J. G. The nuclear magnetic resonance spectrum of ribonuclease. J. Am. Chem. Soc. 79, 3289–3290 (1957).

    Article  CAS  Google Scholar 

  22. Ernst, R. R. & Anderson, W. A. Application of Fourier transform to magnetic resonance. Rev. Sci. Inst. 37, 93–102 (1966).

    Article  CAS  Google Scholar 

  23. Aue, W. P., Bartholdi, E. & Ernst, R. R. Two-dimensional spectroscopy: application to nuclear magnetic resonance. J. Chem. Phys. 64, 2229–2246 (1976).

    Article  CAS  Google Scholar 

  24. Overhauser, A. Polarization of nuclei in metals. Phys. Rev. 92, 411–415 (1953).

    Article  CAS  Google Scholar 

  25. Williamson, M. P., Havel, T. F. & Wüthrich, K. Solution conformation of proteinase inhibitor IIA from bull seminal plasma by 1H nuclear magnetic resonance and distance geometry. J. Mol. Biol. 182, 295–315 (1985).

    Article  CAS  Google Scholar 

  26. Pervushin, K., Riek, R., Wider, G. & Wüthrich, K. Attenuated T2 relaxation by mutual cancellation of dipole–dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules. Proc. Natl Acad. Sci. USA 94, 12366–12371 (1997).

    Article  CAS  Google Scholar 

  27. NMR supplement. Nature Struct. Biol. 5, S492–S522 (1998)

  28. Fu, R. & Cross, T. A. Solid state NMR investigation of protein and polypeptide structure. Annu. Rev. Biophys. Biomol. Struct. 28, 235–268 (1999).

    Article  CAS  Google Scholar 

  29. Alder, B. J. & Wainwright, T. E. Studies in molecular dynamics. I. General method. J. Chem. Phys. 31, 459–466 (1959).

    Article  CAS  Google Scholar 

  30. Rahman, A. & Stillinger, F. H. Molecular dynamics study of liquid water. J. Chem. Phys. 55, 3336–3359 (1971).

    Article  CAS  Google Scholar 

  31. McCammon, J. A., Gelin, B. R. & Karplus, M. Dynamics of folded proteins. Nature 267, 585–590 (1977).

    Article  CAS  Google Scholar 

  32. Wang, W., Donini, O., Reyes, C. M. & Kollman, P. A. Biomolecular simulations: recent developments in force fields, simulations of enzyme catalysis, protein–ligand, protein–protein, and protein–nucleic acid noncovalent interactions. Annu. Rev. Biophys. Biomol. Struct. 30, 211–243 (2001).

    Article  CAS  Google Scholar 

  33. Richards, F. M. The matching of physical models to three-dimensional electron-density maps: a simple optical device. J. Mol. Biol. 37, 225–230 (1968).

    Article  CAS  Google Scholar 

  34. Levinthal, C. Molecular model building by computer. Sci. Am. 214, 42–52 (1966).

    Article  CAS  Google Scholar 

  35. Jones, T. A. A graphics model building and refinement system for macromolecules. J. Appl. Crystallogr. 11, 268–272 (1978).

    Article  CAS  Google Scholar 

  36. Sayle, R. A. & Milner-White, E. J. Biomolecular graphics for all. Trends Biochem. Sci. 20, 374–376 (1995).

    Article  CAS  Google Scholar 

  37. Watson, J. D. & Crick, F. H. C. A structure for deoxyribose nucleic acid. Nature 171, 737–738 (1953).

    Article  CAS  Google Scholar 

  38. Wall, M. E., Gallagher, S. C. & Trewhella, J. Large scale shape changes in proteins and macromolecular complexes. Annu. Rev. Phys. Chem. 51, 355–380 (2000).

    Article  CAS  Google Scholar 

  39. Engel, A. & Muller, D. J. Observing single biomolecules at work with the atomic force microscope. Nature Struct. Biol. 7, 715–718 (2000).

    Article  CAS  Google Scholar 

  40. Knight, A. E., Veigel, C., Chambers, C. & Molloy, J. E. Analysis of single-molecule mechanical recordings: application to acto-myosin interactions. Prog. Biophys. Mol. Biol. 77, 45–72 (2001).

    Article  CAS  Google Scholar 

  41. Minsky, M. Microscopy apparatus. US Patent 3013467 (1961). Filed 7th November 1957.

  42. Moult, J., Fidelis, K., Zemla, A. & Hubbard, T. Critical assessment of methods of protein structure prediction (CASP): round IV. Proteins 45, S2–S7 (2001).

    Article  Google Scholar 

  43. Deisenhofer, J. et al. X-ray structure analysis of a membrane protein complex. J. Mol. Biol. 180, 385–398 (1984).

    Article  CAS  Google Scholar 

  44. Abrahams, J. P., Leslie, A. G. & Lutter, R. Structure at 2.8Å of F1-ATPase from bovine heart mitochondria. Nature 370, 621–628 (1994).

    Article  CAS  Google Scholar 

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Acknowledgements

Perhaps the greatest optimist of them all, Max Perutz, died on 6 February 2002. He lived long enough to see his early optimistic experiments bear extraordinary fruit. I dedicate this article to him. This article is a contribution from the Oxford Centre for Molecular Sciences, which has been supported by the BBSRC, MRC and EPSRC. Support from the Wellcome Trust is also gratefully acknowledged.

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  1. the Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK

    Iain D. Campbell

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  1. Iain D. Campbell
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FURTHER READING

Laboratory of Molecular Biology

Protein Data Bank 

Encyclopedia of Life Sciences

Antoni van Leeuwenhoek

confocal microscopy

electron microscopy

Fred Sanger

Max Perutz

Molecular dynamics

NMR

'phase' problem

solid state NMR

synchotron sources

X-ray diffraction

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Campbell, I. The march of structural biology. Nat Rev Mol Cell Biol 3, 377–381 (2002). https://doi.org/10.1038/nrm800

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