Skip to main content
SpringerLink
Log in

Intrinsically unstructured regions in the C domain of the influenza virus M1 protein

  • Structural and Functional Analysis of Biopolymers and Their Complexes
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

The M1 matrix protein of the influenza virus is one of the main structural components of the virion that performs several different functions in the infected cell. X-ray analysis (with 2.08 Å resolution) has been performed for the N-terminal part of the M1 protein (residues 2–158) but not for its C-terminal domain (159–252). In the present study, we analyzed the structure of the M1 protein of the influenza virus A/Puerto Rico/8/34 (H1N1) strain in acidic solution using tritium planigraphy. The incorporation of tritium label into the domains of the M1 protein were studied; the C domain and the interdomain loops are preferentially accessible to tritium. Analytical centrifugation and dynamic laser light scattering demonstrated anomalous hydrodynamic parameters and low structuredness of the M1 protein, which has also been confirmed by circular dichroism data. Bioinformatic analysis of the M1 protein sequence revealed intrinsically unstructured segments that were concentrated in the C domain and interdomain loops between the N-, M-, and C domains. We suggest that the multifunctionality of the M1 protein in a cell is determined by the plasticity of its tertiary structure, which is caused by the presence of intrinsically unstructured segments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

Flu:

influenza virus

RNP:

ribonucleoproteide

BSA:

bovine serum albumin

IUS:

intrinsically unstructured segments

TP:

tritium planigraphy

CD:

circular dichroism

X-ray:

X-ray structure analysis

AC:

analytical centrifugation

DLS:

dynamic light laser scattering

HA:

hemagglutinin

NA:

neuraminidase

MES:

2-/N-morpholino/-ethanesulphonic acid

References

  1. Fujiyoshi Y., Kume N.P., Sakata K., Sato S. 1994. Fine structure of influenza A virus observed by electron cryomicroscopy. EMBO J. 13, 318–326.

    PubMed  CAS  Google Scholar 

  2. Calder L.J., Wasilewski S., Berriman J.A., Rosental P.B. 2010. Structural organization of a filamentous influenza A virus. Proc. Natl. Acad. Sci. U. S. A. 107, 10685–10690.

    Article  PubMed  CAS  Google Scholar 

  3. Ali A., Avalos R.T., Ponimaskin E., Nayak D.P. 2000. Influenza virus assembly: Effect of influenza virus glycoproteins on the membrane association of M1 protein. J. Virol. 74, 8709–8719.

    Article  PubMed  CAS  Google Scholar 

  4. Whittaker G., Bui M., Helenius A. 1996. The role of nuclear import and export in influenza virus infection. Trends Cell Biol. 6, 67–71.

    Article  PubMed  CAS  Google Scholar 

  5. Avalos R.T., Yu Z., Nayak D.P. 1997. Association of influenza virus NP and M1 proteins with cellular cytoskeletal elements in influenza virus-infected cells. J. Virol. 71, 2947–2958.

    PubMed  CAS  Google Scholar 

  6. Sha B., Luo M. 1997. Structure of a bifunctional membrane-RNA binding protein, influenza virus matrix protein M1. Nature Struct. Biol. 4, 239–244.

    Article  PubMed  CAS  Google Scholar 

  7. Arzt S., Baudin F., Barge A., Timmins P., Burmeister W.P., Ruigrok R.W.H. 2001. Combined results from solution studies on intact influenza virus M1 protein and from a new crystal form of its N-terminal domain show that M1 is an elongated monomer. Virology. 297, 439–446.

    Article  Google Scholar 

  8. Uversky V.N. 2002. Natively unfolded proteins: A point where biology waits for physics. Protein Sci. 11, 739–756.

    Article  PubMed  CAS  Google Scholar 

  9. Serdyuk I.N. 2007. Structured proteins and proteins with intrinsic disorder. Mol. Biol. (Moscow). 41, 262–277.

    Article  CAS  Google Scholar 

  10. Sickmeier M., Hamilton J.A., LeGall T., Vacic V., Cortese M.S., Tantos A., Szabo B., Tompa P., Chen J., Uversky V.N., Obradovic Z., Dunker A.K. 2007. Dis-Prot: The database of disordered proteins. Nucleic Acids Res. 35, 786–793.

    Article  Google Scholar 

  11. Galzitskaya O.V., Garbuzynskiy S.O., Lobanov M.Yu. 2006. Prediction of natively unfolded regions in protein chains. Mol. Biol. (Moscow). 40, 298–304.

    Article  CAS  Google Scholar 

  12. Ferron F., Longhi S., Canard B., Karlin D. 2006. A practical overview of protein disorder prediction methods. Proteins. 65, 1–14.

    Article  PubMed  CAS  Google Scholar 

  13. Shishkov A.V., Gol’danskii V.I., Baratova L.A., Fedorova N.V., Ksenofontov A.L., Zhirnov O.P., Baratova L.A., Galkin A.V. 1999. The in situ spatial arrangement of the influenza A virus matrix protein M1 assessed by tritium bombardment. Proc. Natl. Acad. Sci. U. S. A. 96, 7827–7830.

    Article  PubMed  CAS  Google Scholar 

  14. Bogacheva E.N., Dolgov A.A., Chulichkov A.L., Shishkov A.V., Badun G.A., Ksenofontov A.L., Fedorova N.V., Baratova L.A. 2010. Specific features of M1 protein structure in solution. Perspekt. Materialy. 8, 148–154.

    Google Scholar 

  15. Bogacheva E.N., Gol’danskii V.I., Shishkov A.V., Galkin A.V., Baratova L.A. 1998. Tritium planigraphy: From the accessible surface to the spatial structure of a protein. Proc. Natl. Acad. Sci. U. S. A. 95, 2790–2794.

    Article  PubMed  CAS  Google Scholar 

  16. Zhirnov O.P. 1992. Isolation of matrix protein M1 from influenza viruses by acid-dependent extraction with nonionic detergent. Virology. 186, 324–330.

    Article  PubMed  CAS  Google Scholar 

  17. Dosztanyi Z., Csizmok V.P., Tompa P., Simon I. 2005. IUPred: Web server for the prediction intrinsically unstructured regions of proteins based on estimated energy content. Bioinformatics. 21, 3433–3434.

    Article  PubMed  CAS  Google Scholar 

  18. Ward J.J., McGuffin L.J., Bryson K., Buxton B.F., Jones D.T. 2004. The DISOPRED server for the prediction of protein disorder. Bioinformatics. 20, 2138–2139.

    Article  PubMed  CAS  Google Scholar 

  19. Linding R., Jensen L.J., Diella F., Bork P., Gibson T.J., Russell R.B. 2003. Protein disorder prediction: Implications for structural proteomics. Structure. 11, 1316–1317.

    Article  Google Scholar 

  20. Ishida T., Kinoshita K. 2007. PrDOS: Prediction of disordered protein regions from amino acid sequence. Nucleic Acids Res. 35, 1–5.

    Article  Google Scholar 

  21. Prilusky J., Felder C.E., Mordehai T., Rydberg E., Man O., Beckmann J.S., Silman I., Sussman J.L. 2005. FoldIndex.: A simple tool to predict whether a given protein sequence is intrinsically unfolded. Bioinformatics. 21, 3435–3438.

    Article  PubMed  CAS  Google Scholar 

  22. Sreerama N., Woody R.W. 2004. Computation and analysis of protein circular dichroism spectra. Methods Enzymol. 383, 318–351.

    Article  PubMed  CAS  Google Scholar 

  23. Ksenofontov A.L., Kozlovskii V.S., Kordyukova L.V., Radyukhin V.A., Timofeeva A.V., Dobrov E.N. 2006. Determination of concentration and aggregate size in influenza virus preparations from true UV absorption spectra. Mol. Biol. (Moscow). 40, 152–158.

    Article  CAS  Google Scholar 

  24. Cantor Ch.R., Shimmel P.R. 1984. Biophysical Chemistry. San Francisco: Freeman.

    Google Scholar 

  25. Goh G.K. Dunker A.K., Uversky V.N. 2008. A comparative analysis of viral matrix proteins using disorder predictors. Virol. J. 5, 1–10.

    Article  Google Scholar 

  26. Noton S.L., Medcalf E., Fisher D., Mullin A.E., Elton D., Digard P. 2007. Identification of the domains of the influenza A virus M1 matrix protein required for NP binding, oligomerization and incorporation into virions. J Gen. Virol. 88, 2280–2290.

    Article  PubMed  CAS  Google Scholar 

  27. McCullers J.A., Hoffmann E., Huber V.C., Nickerson A.D. 2005. A single amino acid change in the C-terminal domain of the matrix protein M1 of influenza B virus confers mouse adaptation and virulence. Virology. 336, 318–326.

    Article  PubMed  CAS  Google Scholar 

  28. Kuznetsova M.A., Pekov Yu.A., Ksenofontov A.L., Kordyukova L.V., Drutsa V.L. 2010. Assessment of evolutionary stability of influenza A virus: Prediction of variable regions in the domain structure of the M1 protein. Vestn. Mosk. Gos. Univ. Ser. Biol. 65, no. 4, 222–224.

    Google Scholar 

  29. Harris A., Forouhar F., Qiu S., Sha B., Luo M. 2001. The crystal structure of the influenza matrix protein M1 at neutral pH: M1-M1 protein interfaces can rotate in the oligomeric structures of M1. Virology. 289, 34–44.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, 119199, Russia

    A. L. Ksenofontov, E. N. Dobrov, N. V. Fedorova, V. A. Radyukhin, A. M. Arutyunyan & L. A. Baratova

  2. Chemistry Department, Moscow State University, Moscow, 119199, Russia

    G. A. Badun

  3. Semenov Institute of Chemical Physics, Russian Academy of Science, Moscow, 119991, Russia

    E. N. Bogacheva

Authors
  1. A. L. Ksenofontov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. N. Dobrov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. V. Fedorova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. A. Radyukhin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. A. Badun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. M. Arutyunyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E. N. Bogacheva
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L. A. Baratova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. L. Ksenofontov.

Additional information

Original Russian Text © A.L. Ksenofontov, E.N. Dobrov, N.V. Fedorova, V.A. Radyukhin, G.A. Badun, A.M. Arutyunyan, E.N. Bogacheva, L.A. Baratova, 2011, published in Molekulyarnaya Biologiya, 2011, Vol. 45, No. 4, pp. 689–696.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ksenofontov, A.L., Dobrov, E.N., Fedorova, N.V. et al. Intrinsically unstructured regions in the C domain of the influenza virus M1 protein. Mol Biol 45, 634–640 (2011). https://doi.org/10.1134/S0026893311030071

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893311030071

Keywords

Search

Navigation