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
. 1994 Aug 30;91(18):8442–8446. doi: 10.1073/pnas.91.18.8442

Circular dichroism, molecular modeling, and serology indicate that the structural basis of antigenic variation in foot-and-mouth disease virus is alpha-helix formation.

L L France 1, P G Piatti 1, J F Newman 1, I Toth 1, W A Gibbons 1, F Brown 1
PMCID: PMC44622  PMID: 8078900

Abstract

Seven antigenic variants obtained from a single field isolate of foot-and-mouth disease virus, serotype A12, differ only at residues 148 and 153 in the immunodominant loop of viral protein VP1. Synthetic peptides corresponding to the region 141-160 are highly immunogenic. UV circular dichroism shows that (i) in aqueous solution the peptides are nearly identical, but in 100% trifluoroethanol they display helix-forming properties which correlate well with their serological crossreactivities for anti-peptide sera, and (ii) these properties are insensitive to substitutions at position 153, except for proline, but are highly sensitive to substitutions at position 148. This pattern can be explained by the effects of these substitutions on the amphiphilic character and positions of helices postulated in the region 146-156. Molecular models indicate that residues 147, 148, 150, 151, 153-155, and 157 are most likely to interact with residues of the antibody paratopes. The data are consistent with the existence of an inverse gamma-turn around Pro-153, and a beta-turn at the cell-attachment site at residues 145-147.

Full text

PDF
8442

Images in this article

8445Image
on p.8445

Selected References

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

  1. Acharya R., Fry E., Stuart D., Fox G., Rowlands D., Brown F. The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution. Nature. 1989 Feb 23;337(6209):709–716. doi: 10.1038/337709a0. [DOI] [PubMed] [Google Scholar]
  2. Barlow D. J., Thornton J. M. Helix geometry in proteins. J Mol Biol. 1988 Jun 5;201(3):601–619. doi: 10.1016/0022-2836(88)90641-9. [DOI] [PubMed] [Google Scholar]
  3. Brown F. Use of peptides for immunization against foot-and-mouth disease. Vaccine. 1988 Apr;6(2):180–182. doi: 10.1016/s0264-410x(88)80024-0. [DOI] [PubMed] [Google Scholar]
  4. Chou P. Y., Fasman G. D. Empirical predictions of protein conformation. Annu Rev Biochem. 1978;47:251–276. doi: 10.1146/annurev.bi.47.070178.001343. [DOI] [PubMed] [Google Scholar]
  5. Connolly M. L. Solvent-accessible surfaces of proteins and nucleic acids. Science. 1983 Aug 19;221(4612):709–713. doi: 10.1126/science.6879170. [DOI] [PubMed] [Google Scholar]
  6. Dyson H. J., Rance M., Houghten R. A., Lerner R. A., Wright P. E. Folding of immunogenic peptide fragments of proteins in water solution. I. Sequence requirements for the formation of a reverse turn. J Mol Biol. 1988 May 5;201(1):161–200. doi: 10.1016/0022-2836(88)90446-9. [DOI] [PubMed] [Google Scholar]
  7. Fox G., Parry N. R., Barnett P. V., McGinn B., Rowlands D. J., Brown F. The cell attachment site on foot-and-mouth disease virus includes the amino acid sequence RGD (arginine-glycine-aspartic acid). J Gen Virol. 1989 Mar;70(Pt 3):625–637. doi: 10.1099/0022-1317-70-3-625. [DOI] [PubMed] [Google Scholar]
  8. France L. L., Kieleczawa J., Dunn J. J., Hind G., Sutherland J. C. Structural analysis of an outer surface protein from the Lyme disease spirochete, Borrelia burgdorferi, using circular dichroism and fluorescence spectroscopy. Biochim Biophys Acta. 1992 Mar 27;1120(1):59–68. doi: 10.1016/0167-4838(92)90424-c. [DOI] [PubMed] [Google Scholar]
  9. Gray D. M., Lang D., Kuner E., Vaughan M., Sutherland J. A thin quartz cell suitable for vacuum ultraviolet absorption and circular dichroism measurements. Anal Biochem. 1984 Jan;136(1):247–250. doi: 10.1016/0003-2697(84)90331-2. [DOI] [PubMed] [Google Scholar]
  10. Greenfield N., Fasman G. D. Computed circular dichroism spectra for the evaluation of protein conformation. Biochemistry. 1969 Oct;8(10):4108–4116. doi: 10.1021/bi00838a031. [DOI] [PubMed] [Google Scholar]
  11. Janin J. Surface and inside volumes in globular proteins. Nature. 1979 Feb 8;277(5696):491–492. doi: 10.1038/277491a0. [DOI] [PubMed] [Google Scholar]
  12. Loret E. P., Georgel P., Johnson W. C., Jr, Ho P. S. Circular dichroism and molecular modeling yield a structure for the complex of human immunodeficiency virus type 1 trans-activation response RNA and the binding region of Tat, the trans-acting transcriptional activator. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9734–9738. doi: 10.1073/pnas.89.20.9734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Manavalan P., Johnson W. C., Jr Variable selection method improves the prediction of protein secondary structure from circular dichroism spectra. Anal Biochem. 1987 Nov 15;167(1):76–85. doi: 10.1016/0003-2697(87)90135-7. [DOI] [PubMed] [Google Scholar]
  14. Milner-White E., Ross B. M., Ismail R., Belhadj-Mostefa K., Poet R. One type of gamma-turn, rather than the other gives rise to chain-reversal in proteins. J Mol Biol. 1988 Dec 5;204(3):777–782. doi: 10.1016/0022-2836(88)90368-3. [DOI] [PubMed] [Google Scholar]
  15. Newman J. F., Piatti P. G., Gorman B. M., Burrage T. G., Ryan M. D., Flint M., Brown F. Foot-and-mouth disease virus particles contain replicase protein 3D. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):733–737. doi: 10.1073/pnas.91.2.733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. O'Neil K. T., DeGrado W. F. A thermodynamic scale for the helix-forming tendencies of the commonly occurring amino acids. Science. 1990 Nov 2;250(4981):646–651. doi: 10.1126/science.2237415. [DOI] [PubMed] [Google Scholar]
  17. Padmanabhan S., Marqusee S., Ridgeway T., Laue T. M., Baldwin R. L. Relative helix-forming tendencies of nonpolar amino acids. Nature. 1990 Mar 15;344(6263):268–270. doi: 10.1038/344268a0. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Rowlands D. J., Clarke B. E., Carroll A. R., Brown F., Nicholson B. H., Bittle J. L., Houghten R. A., Lerner R. A. Chemical basis of antigenic variation in foot-and-mouth disease virus. Nature. 1983 Dec 15;306(5944):694–697. doi: 10.1038/306694a0. [DOI] [PubMed] [Google Scholar]
  20. Schiffer M., Edmundson A. B. Correlation of amino acid sequence and conformation in tobacco mosaic virus. Biophys J. 1968 Jan;8(1):29–39. doi: 10.1016/S0006-3495(68)86472-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Scopes R. K. Measurement of protein by spectrophotometry at 205 nm. Anal Biochem. 1974 May;59(1):277–282. doi: 10.1016/0003-2697(74)90034-7. [DOI] [PubMed] [Google Scholar]
  22. Shoemaker K. R., Kim P. S., York E. J., Stewart J. M., Baldwin R. L. Tests of the helix dipole model for stabilization of alpha-helices. Nature. 1987 Apr 9;326(6113):563–567. doi: 10.1038/326563a0. [DOI] [PubMed] [Google Scholar]
  23. Siligardi G., Drake A. F., Mascagni P., Rowlands D., Brown F., Gibbons W. A. Correlations between the conformations elucidated by CD spectroscopy and the antigenic properties of four peptides of the foot-and-mouth disease virus. Eur J Biochem. 1991 Aug 1;199(3):545–551. doi: 10.1111/j.1432-1033.1991.tb16153.x. [DOI] [PubMed] [Google Scholar]
  24. Stanfield R. L., Fieser T. M., Lerner R. A., Wilson I. A. Crystal structures of an antibody to a peptide and its complex with peptide antigen at 2.8 A. Science. 1990 May 11;248(4956):712–719. doi: 10.1126/science.2333521. [DOI] [PubMed] [Google Scholar]
  25. Venkatachalam C. M. Stereochemical criteria for polypeptides and proteins. V. Conformation of a system of three linked peptide units. Biopolymers. 1968 Oct;6(10):1425–1436. doi: 10.1002/bip.1968.360061006. [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