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Structural organization of brain-derived mammalian prions examined by hydrogen-deuterium exchange

Nature Structural & Molecular Biology volume 18, pages 504–506 (2011)Cite this article

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Abstract

One of the mysteries in prion research is the structure of the infectious form of mammalian prion protein PrPSc. Here we used mass spectrometry analysis of hydrogen-deuterium exchange to examine brain-derived PrPSc. Our data indicate that, contrary to popular models, prion-protein conversion involves refolding of the entire region from residue ~80–90 to the C-terminus, which in PrPSc consists of β-strands and relatively short turns and/or loops, with no native α-helices present.

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Figure 1: Deuterium incorporation for peptic fragments derived from different types of misfolded prion-protein aggregates.
Figure 2: Schematic representation of prion-protein secondary structure in the β-helix (B) and spiral (S) models of PrPSc.
Figure 3: Pairwise comparison of difference in deuterium incorporation after 240‐h exchange for different PrPSc strains.

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References

  1. Prusiner, S.B. Proc. Natl. Acad. Sci. USA 95, 13363–13383 (1998).

    Article  CAS  Google Scholar 

  2. Cobb, N.J. & Surewicz, W.K. Biochemistry 48, 2574–2585 (2009).

    Article  CAS  Google Scholar 

  3. Castilla, J., Saa, P., Hetz, C. & Soto, C. Cell 121, 195–206 (2005).

    Article  CAS  Google Scholar 

  4. Deleault, N.R., Harris, B.T., Rees, J.R. & Supattapone, S. Proc. Natl. Acad. Sci. USA 104, 9741–9746 (2007).

    Article  CAS  Google Scholar 

  5. Kim, J.I. et al. J. Biol. Chem. 285, 14083–14087 (2010).

    Article  CAS  Google Scholar 

  6. Wang, F., Wang, X., Yuan, C.G. & Ma, J. Science 327, 1132–1135 (2010).

    Article  CAS  Google Scholar 

  7. Wüthrich, K. & Riek, R. Adv. Protein Chem. 57, 55–82 (2001).

    Article  Google Scholar 

  8. Caughey, B.W. et al. Biochemistry 30, 7672–7680 (1991).

    Article  CAS  Google Scholar 

  9. Safar, J., Roller, P.P., Gajdusek, D.C. & Gibbs, C.J. Jr. Protein Sci. 2, 2206–2216 (1993).

    Article  CAS  Google Scholar 

  10. Gasset, M., Baldwin, M.A., Fletterick, R.J. & Prusiner, S.B. Proc. Natl. Acad. Sci. USA 90, 1–5 (1993).

    Article  CAS  Google Scholar 

  11. Toyama, B.H., Kelly, M.J., Gross, J.D. & Weissman, J.S. Nature 449, 233–237 (2007).

    Article  CAS  Google Scholar 

  12. Lu, X., Wintrode, P.L. & Surewicz, W.K. Proc. Natl. Acad. Sci. USA 104, 1510–1515 (2007).

    Article  CAS  Google Scholar 

  13. Chesebro, B. et al. Science 308, 1435–1439 (2005).

    Article  CAS  Google Scholar 

  14. Cobb, N.J., Sonnichsen, F.D., McHaourab, H. & Surewicz, W.K. Proc. Natl. Acad. Sci. USA 104, 18946–18951 (2007).

    Article  CAS  Google Scholar 

  15. Govaerts, C., Wille, H., Prusiner, S.B. & Cohen, F.E. Proc. Natl. Acad. Sci. USA 101, 8342–8347 (2004).

    Article  CAS  Google Scholar 

  16. Wille, H. et al. Proc. Natl. Acad. Sci. USA 106, 16990–16995 (2009).

    Article  CAS  Google Scholar 

  17. DeMarco, M.L. & Daggett, V. Proc. Natl. Acad. Sci. USA 101, 2293–2298 (2004).

    Article  CAS  Google Scholar 

  18. Spassov, S., Beekes, M. & Naumann, D. Biochim. Biophys. Acta 1760, 1138–1149 (2006).

    Article  CAS  Google Scholar 

  19. Wickner, R.B., Shewmaker, F., Kryndushkin, D. & Edskes, H.K. Bioessays 30, 955–964 (2008).

    Article  CAS  Google Scholar 

  20. Sawaya, M.R. et al. Nature 447, 453–457 (2007).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by US National Institutes of Health grants NS44158, NS38604 and AG14359, and by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases.

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Author notes

  1. Vytautas Smirnovas and Gerald S Baron: These authors contributed equally to this study.

Authors and Affiliations

  1. Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, USA

    Vytautas Smirnovas & Witold K Surewicz

  2. Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA

    Gerald S Baron, Danielle K Offerdahl, Gregory J Raymond & Byron Caughey

Authors
  1. Vytautas Smirnovas
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  2. Gerald S Baron
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  3. Danielle K Offerdahl
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  4. Gregory J Raymond
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  5. Byron Caughey
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  6. Witold K Surewicz
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Contributions

V.S. conducted and analyzed H/D exchange experiments. G.J.R. and D.K.O. did all animal-associated work, from animal inoculations to dissection of brain tissue. G.S.B., D.K.O. and G.J.R. prepared PrPSc samples and carried out their biochemical characterization. B.C. did FTIR experiments. W.K.S. wrote the manuscript and coordinated the entire project. G.S.B., V.S. and B.C. discussed the results and revised the manuscript.

Corresponding author

Correspondence to Witold K Surewicz.

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The authors declare no competing financial interests.

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Supplementary Figures 1–4, Supplementary Methods and Supplementary Discussion (PDF 2703 kb)

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Smirnovas, V., Baron, G., Offerdahl, D. et al. Structural organization of brain-derived mammalian prions examined by hydrogen-deuterium exchange. Nat Struct Mol Biol 18, 504–506 (2011). https://doi.org/10.1038/nsmb.2035

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