Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Mar;86(5):1524–1528. doi: 10.1073/pnas.86.5.1524

Destabilization of an alpha-helix-bundle protein by helix dipoles.

M K Gilson 1, B Honig 1
PMCID: PMC286730  PMID: 2922396

Abstract

The finite difference Poisson-Boltzmann method is used to calculate the electrostatic work of assembling the four alpha-helices of Themiste dyscritum hemerythrin to form the protein's observed antiparallel helical bundle. The calculations account for the interaction of each helix dipole with the high-dielectric solvent as well as for pairwise interactions of the dipoles with each other. We find that the electrostatic work of assembly is dominated by unfavorable changes in dipole-solvent interactions rather than by favorable interactions between antiparallel helices. Furthermore, the electrostatic energy difference between the observed arrangement of helices in hemerythrin and at least one other possible helical arrangement is less than 1 kT. These results suggest that the helix dipole actually destabilizes the helical bundle and that it plays little or no role in producing the observed bundle geometry.

Full text

PDF
1524

Selected References

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

  1. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  2. Chou K. C., Maggiora G. M., Némethy G., Scheraga H. A. Energetics of the structure of the four-alpha-helix bundle in proteins. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4295–4299. doi: 10.1073/pnas.85.12.4295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gilson M. K., Honig B. H. Calculation of electrostatic potentials in an enzyme active site. Nature. 1987 Nov 5;330(6143):84–86. doi: 10.1038/330084a0. [DOI] [PubMed] [Google Scholar]
  4. Gilson M. K., Honig B. H. Energetics of charge-charge interactions in proteins. Proteins. 1988;3(1):32–52. doi: 10.1002/prot.340030104. [DOI] [PubMed] [Google Scholar]
  5. Gilson M. K., Honig B. H. The dielectric constant of a folded protein. Biopolymers. 1986 Nov;25(11):2097–2119. doi: 10.1002/bip.360251106. [DOI] [PubMed] [Google Scholar]
  6. Gilson M. K., Honig B. Calculation of the total electrostatic energy of a macromolecular system: solvation energies, binding energies, and conformational analysis. Proteins. 1988;4(1):7–18. doi: 10.1002/prot.340040104. [DOI] [PubMed] [Google Scholar]
  7. Hol W. G., Halie L. M., Sander C. Dipoles of the alpha-helix and beta-sheet: their role in protein folding. Nature. 1981 Dec 10;294(5841):532–536. doi: 10.1038/294532a0. [DOI] [PubMed] [Google Scholar]
  8. Hol W. G. The role of the alpha-helix dipole in protein function and structure. Prog Biophys Mol Biol. 1985;45(3):149–195. doi: 10.1016/0079-6107(85)90001-x. [DOI] [PubMed] [Google Scholar]
  9. Hol W. G., van Duijnen P. T., Berendsen H. J. The alpha-helix dipole and the properties of proteins. Nature. 1978 Jun 8;273(5662):443–446. doi: 10.1038/273443a0. [DOI] [PubMed] [Google Scholar]
  10. Klapper I., Hagstrom R., Fine R., Sharp K., Honig B. Focusing of electric fields in the active site of Cu-Zn superoxide dismutase: effects of ionic strength and amino-acid modification. Proteins. 1986 Sep;1(1):47–59. doi: 10.1002/prot.340010109. [DOI] [PubMed] [Google Scholar]
  11. McCammon J. A., Wolynes P. G., Karplus M. Picosecond dynamics of tyrosine side chains in proteins. Biochemistry. 1979 Mar 20;18(6):927–942. doi: 10.1021/bi00573a001. [DOI] [PubMed] [Google Scholar]
  12. Richards F. M. Areas, volumes, packing and protein structure. Annu Rev Biophys Bioeng. 1977;6:151–176. doi: 10.1146/annurev.bb.06.060177.001055. [DOI] [PubMed] [Google Scholar]
  13. Rogers N. K., Moore G. R., Sternberg M. J. Electrostatic interactions in globular proteins: calculation of the pH dependence of the redox potential of cytochrome c551. J Mol Biol. 1985 Apr 20;182(4):613–616. doi: 10.1016/0022-2836(85)90248-7. [DOI] [PubMed] [Google Scholar]
  14. Rogers N. K., Sternberg M. J. Electrostatic interactions in globular proteins. Different dielectric models applied to the packing of alpha-helices. J Mol Biol. 1984 Apr 15;174(3):527–542. doi: 10.1016/0022-2836(84)90334-6. [DOI] [PubMed] [Google Scholar]
  15. Sheridan R. P., Levy R. M., Salemme F. R. alpha-Helix dipole model and electrostatic stabilization of 4-alpha-helical proteins. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4545–4549. doi: 10.1073/pnas.79.15.4545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sternberg M. J., Hayes F. R., Russell A. J., Thomas P. G., Fersht A. R. Prediction of electrostatic effects of engineering of protein charges. Nature. 1987 Nov 5;330(6143):86–88. doi: 10.1038/330086a0. [DOI] [PubMed] [Google Scholar]
  17. Wada A. The alpha-helix as an electric macro-dipole. Adv Biophys. 1976:1–63. [PubMed] [Google Scholar]
  18. Warshel A. What about protein polarity? Nature. 1987 Nov 5;330(6143):15–16. doi: 10.1038/330015a0. [DOI] [PubMed] [Google Scholar]
  19. Warwicker J., Watson H. C. Calculation of the electric potential in the active site cleft due to alpha-helix dipoles. J Mol Biol. 1982 Jun 5;157(4):671–679. doi: 10.1016/0022-2836(82)90505-8. [DOI] [PubMed] [Google Scholar]
  20. Weber P. C., Salemme F. R. Structural and functional diversity in 4-alpha-helical proteins. Nature. 1980 Sep 4;287(5777):82–84. doi: 10.1038/287082a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES