1887

Abstract

The leader (L) proteinases of aphthoviruses (foot- and-mouth disease viruses) and equine rhinovirus serotypes 1 and 2 cleave themselves from the growing polyprotein. This cleavage occurs intramolecularly between the C terminus of the L proteinases and the N terminus of the subsequent protein VP4. The foot-and-mouth disease virus enzyme has been shown, in addition, to cleave at least one cellular protein, the eukaryotic initiation factor 4G. Mechanistically, inhibitor studies and sequence analysis have been used to classify the L proteinases as papain-like cysteine proteinases. However, sequence identity within the L proteinases themselves is low (between 18% and 32%) and only 14% between the L proteinases and papain. Secondary structure predictions, sequence alignments that take into account the positions of the essential catalytic residues, and structural considerations have been used in this study to investigate more closely the relationships between the L proteinases and papain. In spite of the low sequence identities, the analyses strongly suggest that the L proteinases of foot-and-mouth disease virus and of equine rhinovirus 1 have a similar overall fold to that of papain. Regions in the L proteinases corresponding to all five α-helices and seven β-sheets of papain could be identified. Further comparisons with the proteinase bleomycin hydrolase, which also displays a papain topology in spite of important differences in size and amino acid sequence, support these conclusions and suggest how a C-terminal extension, present in all three L proteinases, and predicted to be an α-helix, might enable C-terminal selfprocessing to occur.

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1998-02-01
2021-10-27
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References

  1. Allaire M., Chernaia M., Malcolm B. A., James M. N. G. 1994; Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin- like serine proteinases. Nature 369:72–76
    [Google Scholar]
  2. Bazan J. F., Fletterick R. J. 1989; Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications. Proceedings of the National Academy of Sciences, USA 85:7872–7876
    [Google Scholar]
  3. Berti P., Storer A. C. 1995; Alignment/phylogeny of the papain superfamily of cysteine proteinases. Journal of Molecular Biology 246:273–283
    [Google Scholar]
  4. Cao X., Bergmann I. E., Füllkrug R., Beck E. 1995; Functional analysis of the two alternative translation initiation sites of foot-and- mouth disease virus. Journal of Virology 69:560–563
    [Google Scholar]
  5. Devaney M. A., Vakharia V. N., Lloyd R. E., Ehrenfeld E., Grubman M. J. 1988; Leader protein of foot-and-mouth disease virus is required for cleavage of the p220 component of the cap-binding protein complex. Journal of Virology 62:4407–4409
    [Google Scholar]
  6. Gorbalenya A. E., Donchenko A. P., Blinov V. M., Koonin E. V. 1989; Cysteine proteases of positive strand RNA viruses and chymotrypsin-like serine proteases. A distinct protein superfamily with a common structural fold. FEBS Letters 243:103–114
    [Google Scholar]
  7. Gorbalenya A. E., Koonin E. V., Lai M. M. 1991; Putative papain- related thiol proteases of positive-strand RNA viruses. Identification of rubi- and aphthovirus proteases and delineation of a novel conserved domain associated with proteases of rubi-, alpha- and coronaviruses. FEBS Letters 288:201–205
    [Google Scholar]
  8. Guarné A., Kirchweger R., Verdaguer R., Liebig H.-D., Blaas D., Skern T., Fita I. 1996; Crystallization and preliminary X-ray diffraction studies of the Lb proteinase of foot-and-mouth disease virus. Protein Science 5:1931–1933
    [Google Scholar]
  9. Joshua-Tor L., Xu H. E., Johnston S. A., Rees D. C. 1995; Crystal structure of a conserved protease that binds DNA: the bleomycin hydrolase, Gal6. Science 269:945–950
    [Google Scholar]
  10. Kamphuis I. G., Kalk K. H., Swarte M. B. A., Drenth J. 1984; Structure of papain refined at 1·65Å resolution. Journal of Molecular Biology 179:233–256
    [Google Scholar]
  11. Kirchweger R., Ziegler E., Lamphear B. J., Waters D., Liebig H. D., Sommergruber W., Sobrino F., Hohenadl C., Blaas D., Rhoads R. E., Skern T. 1994; Foot-and-mouth disease virus leader proteinase: purification of the Lb form and determination of its cleavage site on elF-4y. Journal of Virology 68:5677–5684
    [Google Scholar]
  12. Kleina L. G., Grubman M. J. 1992; Antiviral effects of a thiol protease inhibitor on foot-and-mouth disease virus. Journal of Virology 66:7168–7175
    [Google Scholar]
  13. Kraulis P. J. 1991; MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. Journal of Applied Crystallography 24:946–950
    [Google Scholar]
  14. Lamphear B. J., Kirchweger G., Skern T., Rhoads R. R. 1995; Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Journal of Biological Chemistry 270:21975–21983
    [Google Scholar]
  15. Matthews D. A., Smith W. W., Ferre R. A., Condon B., Budahazi G., Sisson W., Villafranca J. E., Janson C. A., McElroy H. E., Gribskov C. L., Worland S. 1994; Structure of human rhinovirus 3C protease reveals a trypsin-like polypeptide fold, RNA-binding site, and means for cleaving precursor polyprotein. Cell 77:761–771
    [Google Scholar]
  16. Piccone M. E., Zellner M., Kumosinski T. F., Mason P. W., Grubman M. J. 1995; Identification of the active-site residues of the L proteinase of foot-and-mouth disease virus. Journal of Virology 69:4950–4956
    [Google Scholar]
  17. Roberts P. J., Belsham G. J. 1995; Identification of critical amino acids within the foot-and-mouth disease virus leader protein, a cysteine protease. Virology 213:140–146
    [Google Scholar]
  18. Rost B. 1996; PHD: predicting one-dimensional protein structure by profile based neural networks. Methods in Enzymology 266:525–539
    [Google Scholar]
  19. Rost B., Sander C. 1993; Prediction of protein structure at better than 70% accuracy. Journal of Molecular Biology 232:584–599
    [Google Scholar]
  20. Sangar D. V., Newton S. E., Rowlands D. J., Clarke B. E. 1987; All foot and mouth disease virus serotypes initiate protein synthesis at two separate AUGs. Nucleic Acids Research 15:3305–3315
    [Google Scholar]
  21. Wutz G., Auer H., Nowotny N., Grosse B., Skern T., Kuechler E. 1996; Equine rhinovirus serotypes 1 and 2 : relationship to each other and to aphthoviruses and cardioviruses. Journal of General Virology 77:1719–1730
    [Google Scholar]
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