Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1985 Oct 1;231(1):1–10. doi: 10.1042/bj2310001

The study of conformational states of proteins by nuclear magnetic resonance.

I D Campbell, C M Dobson, R J Williams
PMCID: PMC1152695  PMID: 2998335

Abstract

By the use of examples, mainly of rather rigid proteins, we hope to have shown that conformational analysis of proteins is a problem that is not simply related to the conformational analysis of small molecules. The primary difficulties with proteins are (1) the multitude of possible conformers, (2) the complex dynamical behaviour and (3) the degree of co-operativity within the molecules. Any experimentally derived structural description of a protein is an attempt to represent some average of a complex time dependence. N.m.r. techniques have now reached the point where it is possible to use them to describe many detailed structural features of small globular proteins in solution and to detect and to describe conformational changes in such proteins. In addition, analysis is becoming possible of much less ordered regions of polypeptides, such as are found in less compact proteins, of for example myosin, histones and virus coat proteins, or in denatured states. The limits to the detailed conformational analysis of such proteins are likely to be ones of reality rather than method but the description of the properties shown in Table 1 is by its very nature an extremely important problem in conformational analysis of dynamic macromolecules.

Full text

PDF
(iv)

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barry C. D., North A. C., Glasel J. A., Williams R. J., Xavier A. V. Quantitative determination of mononucleotide conformations in solution using lanthanide ion shift and broadenine NMR probes. Nature. 1971 Jul 23;232(5308):236–245. doi: 10.1038/232236a0. [DOI] [PubMed] [Google Scholar]
  2. Benz F. W., Roberts G. C. Nucler magnetic resonance studies of the unfolding of pancreatic ribonuclease. J Mol Biol. 1975 Jan 25;91(3):345–365. doi: 10.1016/0022-2836(75)90385-x. [DOI] [PubMed] [Google Scholar]
  3. Birdsall B., Bevan A. W., Pascual C., Roberts G. C., Feeney J., Gronenborn A., Clore G. M. Multinuclear NMR characterization of two coexisting conformational states of the Lactobacillus casei dihydrofolate reductase-trimethoprim-NADP+ complex. Biochemistry. 1984 Sep 25;23(20):4733–4742. doi: 10.1021/bi00315a032. [DOI] [PubMed] [Google Scholar]
  4. Campbell I. D., Dobson C. M., Moore G. R., Perkins S. J., Williams R. J. Temperature dependent molecular motion of a tyrosine residue of ferrocytochrome C. FEBS Lett. 1976 Nov;70(1):96–100. doi: 10.1016/0014-5793(76)80734-x. [DOI] [PubMed] [Google Scholar]
  5. Campbell I. D., Dobson C. M. The application of high resolution nuclear magnetic resonance to biological systems. Methods Biochem Anal. 1979;25:1–133. doi: 10.1002/9780470110454.ch1. [DOI] [PubMed] [Google Scholar]
  6. Clore G. M., Gronenborn A. M., Birdsall B., Feeney J., Roberts G. C. 19F-n.m.r. studies of 3',5'-difluoromethotrexate binding to Lactobacillus casei dihydrofolate reductase. Molecular motion and coenzyme-induced conformational changes. Biochem J. 1984 Feb 1;217(3):659–666. doi: 10.1042/bj2170659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cook K. H., Schmid F. X., Baldwin R. L. Role of proline isomerization in folding of ribonuclease A at low temperatures. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6157–6161. doi: 10.1073/pnas.76.12.6157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dalgarno D. C., Levine B. A., Williams R. J. Structural information from NMR secondary chemical shifts of peptide alpha C-H protons in proteins. Biosci Rep. 1983 May;3(5):443–452. doi: 10.1007/BF01121955. [DOI] [PubMed] [Google Scholar]
  9. Delepierre M., Dobson C. M., Howarth M. A., Poulsen F. M. Identification using 1H NMR spectroscopy of slowly exchanging amide hydrogens of hen lysozyme in solution. Eur J Biochem. 1984 Dec 3;145(2):389–395. doi: 10.1111/j.1432-1033.1984.tb08566.x. [DOI] [PubMed] [Google Scholar]
  10. Dobson C. M., Evans P. A., Williamson K. L. Proton NMR studies of denatured lysozyme. FEBS Lett. 1984 Mar 26;168(2):331–334. doi: 10.1016/0014-5793(84)80273-2. [DOI] [PubMed] [Google Scholar]
  11. Dobson C. M., Williams R. J. An NMR study of the dynamics of inhibitor-induced conformational changes in lysozyme. FEBS Lett. 1975 Aug 15;56(2):362–365. doi: 10.1016/0014-5793(75)81128-8. [DOI] [PubMed] [Google Scholar]
  12. Englander S. W., Kallenbach N. R. Hydrogen exchange and structural dynamics of proteins and nucleic acids. Q Rev Biophys. 1983 Nov;16(4):521–655. doi: 10.1017/s0033583500005217. [DOI] [PubMed] [Google Scholar]
  13. Hoch J. C., Dobson C. M., Karplus M. Fluctuations and averaging of proton chemical shifts in the bovine pancreatic trypsin inhibitor. Biochemistry. 1982 Mar 16;21(6):1118–1125. doi: 10.1021/bi00535a002. [DOI] [PubMed] [Google Scholar]
  14. Inagaki F., Boyd J., Campbell I. D., Clayden N. J., Hull W. E., Tamiya N., Williams R. J. Dynamics of erabutoxin b as studied by nuclear magnetic resonance. Relaxation studies of methyl proton resonances. Eur J Biochem. 1982 Jan;121(3):609–616. doi: 10.1111/j.1432-1033.1982.tb05829.x. [DOI] [PubMed] [Google Scholar]
  15. Jardetzky O. On the nature of molecular conformations inferred from high-resolution NMR. Biochim Biophys Acta. 1980 Feb 27;621(2):227–232. doi: 10.1016/0005-2795(80)90174-9. [DOI] [PubMed] [Google Scholar]
  16. Kaptein R., Zuiderweg E. R., Scheek R. M., Boelens R., van Gunsteren W. F. A protein structure from nuclear magnetic resonance data. lac repressor headpiece. J Mol Biol. 1985 Mar 5;182(1):179–182. doi: 10.1016/0022-2836(85)90036-1. [DOI] [PubMed] [Google Scholar]
  17. Kim P. S., Baldwin R. L. Specific intermediates in the folding reactions of small proteins and the mechanism of protein folding. Annu Rev Biochem. 1982;51:459–489. doi: 10.1146/annurev.bi.51.070182.002331. [DOI] [PubMed] [Google Scholar]
  18. Moore G. R., Robinson M. N., Williams G., Williams R. J. Solution structure of mitochondrial cytochrome c. II. 1H nuclear magnetic resonance of ferrocytochrome c. J Mol Biol. 1985 Jun 5;183(3):429–446. doi: 10.1016/0022-2836(85)90012-9. [DOI] [PubMed] [Google Scholar]
  19. Pardi A., Billeter M., Wüthrich K. Calibration of the angular dependence of the amide proton-C alpha proton coupling constants, 3JHN alpha, in a globular protein. Use of 3JHN alpha for identification of helical secondary structure. J Mol Biol. 1984 Dec 15;180(3):741–751. doi: 10.1016/0022-2836(84)90035-4. [DOI] [PubMed] [Google Scholar]
  20. Pardi A., Wagner G., Wüthrich K. Protein conformation and proton nuclear-magnetic-resonance chemical shifts. Eur J Biochem. 1983 Dec 15;137(3):445–454. doi: 10.1111/j.1432-1033.1983.tb07848.x. [DOI] [PubMed] [Google Scholar]
  21. Poulsen F. M., Hoch J. C., Dobson C. M. A structural study of the hydrophobic box region of lysozyme in solution using nuclear Overhauser effects. Biochemistry. 1980 Jun 10;19(12):2597–2607. doi: 10.1021/bi00553a011. [DOI] [PubMed] [Google Scholar]
  22. Richarz R., Nagayama K., Wüthrich K. Carbon-13 nuclear magnetic resonance relaxation studies of internal mobility of the polypeptide chain in basic pancreatic trypsin inhibitor and a selectively reduced analogue. Biochemistry. 1980 Nov 11;19(23):5189–5196. doi: 10.1021/bi00564a006. [DOI] [PubMed] [Google Scholar]
  23. Steitz T. A., Harrison R., Weber I. T., Leahy M. Ligand-induced conformational changes in proteins. Ciba Found Symp. 1983;93:25–46. doi: 10.1002/9780470720752.ch3. [DOI] [PubMed] [Google Scholar]
  24. Takano T., Dickerson R. E. Conformation change of cytochrome c. I. Ferrocytochrome c structure refined at 1.5 A resolution. J Mol Biol. 1981 Nov 25;153(1):79–94. doi: 10.1016/0022-2836(81)90528-3. [DOI] [PubMed] [Google Scholar]
  25. Wagner G. Characterization of the distribution of internal motions in the basic pancreatic trypsin inhibitor using a large number of internal NMR probes. Q Rev Biophys. 1983 Feb;16(1):1–57. doi: 10.1017/s0033583500004911. [DOI] [PubMed] [Google Scholar]
  26. Wagner G., Wüthrich K. Sequential resonance assignments in protein 1H nuclear magnetic resonance spectra. Basic pancreatic trypsin inhibitor. J Mol Biol. 1982 Mar 5;155(3):347–366. doi: 10.1016/0022-2836(82)90009-2. [DOI] [PubMed] [Google Scholar]
  27. Wedin R. E., Delepierre M., Dobson C. M., Poulsen F. M. Mechanisms of hydrogen exchange in proteins from nuclear magnetic resonance studies of individual tryptophan indole NH hydrogens in lysozyme. Biochemistry. 1982 Mar 2;21(5):1098–1103. doi: 10.1021/bi00534a042. [DOI] [PubMed] [Google Scholar]
  28. Williams R. J. The conformation properties of proteins in solution. Biol Rev Camb Philos Soc. 1979 Nov;54(4):389–437. doi: 10.1111/j.1469-185x.1979.tb00843.x. [DOI] [PubMed] [Google Scholar]
  29. 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. 1985 Mar 20;182(2):295–315. doi: 10.1016/0022-2836(85)90347-x. [DOI] [PubMed] [Google Scholar]
  30. Woodward C., Simon I., Tüchsen E. Hydrogen exchange and the dynamic structure of proteins. Mol Cell Biochem. 1982 Oct 29;48(3):135–160. doi: 10.1007/BF00421225. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES