Skip to main content
NCBI home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1994 Oct;3(10):1651–1669. doi: 10.1002/pro.5560031005

Role and mechanism of the maturation cleavage of VP0 in poliovirus assembly: structure of the empty capsid assembly intermediate at 2.9 A resolution.

R Basavappa 1, R Syed 1, O Flore 1, J P Icenogle 1, D J Filman 1, J M Hogle 1
PMCID: PMC2142606  PMID: 7849583

Abstract

The crystal structure of the P1/Mahoney poliovirus empty capsid has been determined at 2.9 A resolution. The empty capsids differ from mature virions in that they lack the viral RNA and have yet to undergo a stabilizing maturation cleavage of VP0 to yield the mature capsid proteins VP4 and VP2. The outer surface and the bulk of the protein shell are very similar to those of the mature virion. The major differences between the 2 structures are focused in a network formed by the N-terminal extensions of the capsid proteins on the inner surface of the shell. In the empty capsids, the entire N-terminal extension of VP1, as well as portions corresponding to VP4 and the N-terminal extension of VP2, are disordered, and many stabilizing interactions that are present in the mature virion are missing. In the empty capsid, the VP0 scissile bond is located some 20 A away from the positions in the mature virion of the termini generated by VP0 cleavage. The scissile bond is located on the rim of a trefoil-shaped depression in the inner surface of the shell that is highly reminiscent of an RNA binding site in bean pod mottle virus. The structure suggests plausible (and ultimately testable) models for the initiation of encapsidation, for the RNA-dependent autocatalytic cleavage of VP0, and for the role of the cleavage in establishing the ordered N-terminal network and in generating stable virions.

Full Text

The Full Text of this article is available as a PDF (19.2 MB).

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. Andino R., Rieckhof G. E., Achacoso P. L., Baltimore D. Poliovirus RNA synthesis utilizes an RNP complex formed around the 5'-end of viral RNA. EMBO J. 1993 Sep;12(9):3587–3598. doi: 10.1002/j.1460-2075.1993.tb06032.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arnold E., Luo M., Vriend G., Rossmann M. G., Palmenberg A. C., Parks G. D., Nicklin M. J., Wimmer E. Implications of the picornavirus capsid structure for polyprotein processing. Proc Natl Acad Sci U S A. 1987 Jan;84(1):21–25. doi: 10.1073/pnas.84.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen Z. G., Stauffacher C., Li Y., Schmidt T., Bomu W., Kamer G., Shanks M., Lomonossoff G., Johnson J. E. Protein-RNA interactions in an icosahedral virus at 3.0 A resolution. Science. 1989 Jul 14;245(4914):154–159. doi: 10.1126/science.2749253. [DOI] [PubMed] [Google Scholar]
  5. Compton S. R., Nelsen B., Kirkegaard K. Temperature-sensitive poliovirus mutant fails to cleave VP0 and accumulates provirions. J Virol. 1990 Sep;64(9):4067–4075. doi: 10.1128/jvi.64.9.4067-4075.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Couderc T., Hogle J., Le Blay H., Horaud F., Blondel B. Molecular characterization of mouse-virulent poliovirus type 1 Mahoney mutants: involvement of residues of polypeptides VP1 and VP2 located on the inner surface of the capsid protein shell. J Virol. 1993 Jul;67(7):3808–3817. doi: 10.1128/jvi.67.7.3808-3817.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Evans S. V. SETOR: hardware-lighted three-dimensional solid model representations of macromolecules. J Mol Graph. 1993 Jun;11(2):134-8, 127-8. doi: 10.1016/0263-7855(93)87009-t. [DOI] [PubMed] [Google Scholar]
  8. Fernandez-Tomas C. B., Guttman N., Baltimore D. Morphogenesis of poliovirus 3. Formation of provirion in cell-free extracts. J Virol. 1973 Nov;12(5):1181–1183. doi: 10.1128/jvi.12.5.1181-1183.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Filman D. J., Syed R., Chow M., Macadam A. J., Minor P. D., Hogle J. M. Structural factors that control conformational transitions and serotype specificity in type 3 poliovirus. EMBO J. 1989 May;8(5):1567–1579. doi: 10.1002/j.1460-2075.1989.tb03541.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ghendon Y., Yakobson E., Mikhejeva A. Study of some stages of poliovirus morphogenesis in MiO cells. J Virol. 1972 Aug;10(2):261–266. doi: 10.1128/jvi.10.2.261-266.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Grant R. A., Hiremath C. N., Filman D. J., Syed R., Andries K., Hogle J. M. Structures of poliovirus complexes with anti-viral drugs: implications for viral stability and drug design. Curr Biol. 1994 Sep 1;4(9):784–797. doi: 10.1016/s0960-9822(00)00176-7. [DOI] [PubMed] [Google Scholar]
  12. Guttman N., Baltimore D. Morphogenesis of poliovirus. IV. existence of particles sedimenting at 150S and having the properties of provirion. J Virol. 1977 Aug;23(2):363–367. doi: 10.1128/jvi.23.2.363-367.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Harber J. J., Bradley J., Anderson C. W., Wimmer E. Catalysis of poliovirus VP0 maturation cleavage is not mediated by serine 10 of VP2. J Virol. 1991 Jan;65(1):326–334. doi: 10.1128/jvi.65.1.326-334.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hogle J. M., Chow M., Filman D. J. Three-dimensional structure of poliovirus at 2.9 A resolution. Science. 1985 Sep 27;229(4720):1358–1365. doi: 10.1126/science.2994218. [DOI] [PubMed] [Google Scholar]
  15. Holland J. J., Kiehn E. D. Specific cleavage of viral proteins as steps in the synthesis and maturation of enteroviruses. Proc Natl Acad Sci U S A. 1968 Jul;60(3):1015–1022. doi: 10.1073/pnas.60.3.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Icenogle J., Gilbert S. F., Grieves J., Anderegg J., Rueckert R. A neutralizing monoclonal antibody against poliovirus and its reaction with related antigens. Virology. 1981 Nov;115(1):211–215. doi: 10.1016/0042-6822(81)90103-3. [DOI] [PubMed] [Google Scholar]
  17. Jacobson M. F., Asso J., Baltimore D. Further evidence on the formation of poliovirus proteins. J Mol Biol. 1970 May 14;49(3):657–669. doi: 10.1016/0022-2836(70)90289-5. [DOI] [PubMed] [Google Scholar]
  18. Jacobson M. F., Baltimore D. Morphogenesis of poliovirus. I. Association of the viral RNA with coat protein. J Mol Biol. 1968 Apr 28;33(2):369–378. doi: 10.1016/0022-2836(68)90195-2. [DOI] [PubMed] [Google Scholar]
  19. Jacobson M. F., Baltimore D. Polypeptide cleavages in the formation of poliovirus proteins. Proc Natl Acad Sci U S A. 1968 Sep;61(1):77–84. doi: 10.1073/pnas.61.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jones T. A. Diffraction methods for biological macromolecules. Interactive computer graphics: FRODO. Methods Enzymol. 1985;115:157–171. doi: 10.1016/0076-6879(85)15014-7. [DOI] [PubMed] [Google Scholar]
  21. Kim S. S., Smith T. J., Chapman M. S., Rossmann M. C., Pevear D. C., Dutko F. J., Felock P. J., Diana G. D., McKinlay M. A. Crystal structure of human rhinovirus serotype 1A (HRV1A). J Mol Biol. 1989 Nov 5;210(1):91–111. doi: 10.1016/0022-2836(89)90293-3. [DOI] [PubMed] [Google Scholar]
  22. Luo M., He C., Toth K. S., Zhang C. X., Lipton H. L. Three-dimensional structure of Theiler murine encephalomyelitis virus (BeAn strain). Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2409–2413. doi: 10.1073/pnas.89.6.2409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Luo M., Vriend G., Kamer G., Minor I., Arnold E., Rossmann M. G., Boege U., Scraba D. G., Duke G. M., Palmenberg A. C. The atomic structure of Mengo virus at 3.0 A resolution. Science. 1987 Jan 9;235(4785):182–191. doi: 10.1126/science.3026048. [DOI] [PubMed] [Google Scholar]
  24. Macadam A. J., Ferguson G., Arnold C., Minor P. D. An assembly defect as a result of an attenuating mutation in the capsid proteins of the poliovirus type 3 vaccine strain. J Virol. 1991 Oct;65(10):5225–5231. doi: 10.1128/jvi.65.10.5225-5231.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Marongiu M. E., Pani A., Corrias M. V., Sau M., La Colla P. Poliovirus morphogenesis. I. Identification of 80S dissociable particles and evidence for the artifactual production of procapsids. J Virol. 1981 Aug;39(2):341–347. doi: 10.1128/jvi.39.2.341-347.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Minor P. D., Dunn G., Evans D. M., Magrath D. I., John A., Howlett J., Phillips A., Westrop G., Wareham K., Almond J. W. The temperature sensitivity of the Sabin type 3 vaccine strain of poliovirus: molecular and structural effects of a mutation in the capsid protein VP3. J Gen Virol. 1989 May;70(Pt 5):1117–1123. doi: 10.1099/0022-1317-70-5-1117. [DOI] [PubMed] [Google Scholar]
  27. Molla A., Paul A. V., Wimmer E. Cell-free, de novo synthesis of poliovirus. Science. 1991 Dec 13;254(5038):1647–1651. doi: 10.1126/science.1661029. [DOI] [PubMed] [Google Scholar]
  28. Moss E. G., Racaniello V. R. Host range determinants located on the interior of the poliovirus capsid. EMBO J. 1991 May;10(5):1067–1074. doi: 10.1002/j.1460-2075.1991.tb08046.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Oliveira M. A., Zhao R., Lee W. M., Kremer M. J., Minor I., Rueckert R. R., Diana G. D., Pevear D. C., Dutko F. J., McKinlay M. A. The structure of human rhinovirus 16. Structure. 1993 Sep 15;1(1):51–68. doi: 10.1016/0969-2126(93)90008-5. [DOI] [PubMed] [Google Scholar]
  30. Oppermann H., Koch G. Kinetics of poliovirus replication in HeLa cells infected by isolated RNA. Biochem Biophys Res Commun. 1973 May 15;52(2):635–640. doi: 10.1016/0006-291x(73)90760-2. [DOI] [PubMed] [Google Scholar]
  31. Pallansch M. A., Kew O. M., Semler B. L., Omilianowski D. R., Anderson C. W., Wimmer E., Rueckert R. R. Protein processing map of poliovirus. J Virol. 1984 Mar;49(3):873–880. doi: 10.1128/jvi.49.3.873-880.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Palmenberg A. C. In vitro synthesis and assembly of picornaviral capsid intermediate structures. J Virol. 1982 Dec;44(3):900–906. doi: 10.1128/jvi.44.3.900-906.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Palmenberg A. C. Proteolytic processing of picornaviral polyprotein. Annu Rev Microbiol. 1990;44:603–623. doi: 10.1146/annurev.mi.44.100190.003131. [DOI] [PubMed] [Google Scholar]
  34. Phillips B. A., Summers D. F., Maizel J. V., Jr In vitro assembly of poliovirus-related particles. Virology. 1968 Jun;35(2):216–226. doi: 10.1016/0042-6822(68)90262-6. [DOI] [PubMed] [Google Scholar]
  35. Racaniello V. R., Baltimore D. Cloned poliovirus complementary DNA is infectious in mammalian cells. Science. 1981 Nov 20;214(4523):916–919. doi: 10.1126/science.6272391. [DOI] [PubMed] [Google Scholar]
  36. Rombaut B., Vrijsen R., Brioen P., Boeyé A. A pH-dependent antigenic conversion of empty capsids of poliovirus studied with the aid of monoclonal antibodies to N and H antigen. Virology. 1982 Oct 15;122(1):215–218. doi: 10.1016/0042-6822(82)90393-2. [DOI] [PubMed] [Google Scholar]
  37. Rossmann M. G., Arnold E., Erickson J. W., Frankenberger E. A., Griffith J. P., Hecht H. J., Johnson J. E., Kamer G., Luo M., Mosser A. G. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature. 1985 Sep 12;317(6033):145–153. doi: 10.1038/317145a0. [DOI] [PubMed] [Google Scholar]
  38. Smith T. J., Kremer M. J., Luo M., Vriend G., Arnold E., Kamer G., Rossmann M. G., McKinlay M. A., Diana G. D., Otto M. J. The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating. Science. 1986 Sep 19;233(4770):1286–1293. doi: 10.1126/science.3018924. [DOI] [PubMed] [Google Scholar]
  39. Watanabe Y., Watanabe K., Katagiri S., Hinuma Y. Virus-specific proteins produced in HeLa cells infected with poliovirus: characterization of subunit-like protein. J Biochem. 1965 Jun;57(6):733–741. doi: 10.1093/oxfordjournals.jbchem.a128139. [DOI] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES