Brief Communication | Published:

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

Nature Structural & Molecular Biology volume 18, pages 504506 (2011) | Download Citation

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Proc. Natl. Acad. Sci. USA 95, 13363–13383 (1998).

  2. 2.

    & Biochemistry 48, 2574–2585 (2009).

  3. 3.

    , , & Cell 121, 195–206 (2005).

  4. 4.

    , , & Proc. Natl. Acad. Sci. USA 104, 9741–9746 (2007).

  5. 5.

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

  6. 6.

    , , & Science 327, 1132–1135 (2010).

  7. 7.

    & Adv. Protein Chem. 57, 55–82 (2001).

  8. 8.

    et al. Biochemistry 30, 7672–7680 (1991).

  9. 9.

    , , & Protein Sci. 2, 2206–2216 (1993).

  10. 10.

    , , & Proc. Natl. Acad. Sci. USA 90, 1–5 (1993).

  11. 11.

    , , & Nature 449, 233–237 (2007).

  12. 12.

    , & Proc. Natl. Acad. Sci. USA 104, 1510–1515 (2007).

  13. 13.

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

  14. 14.

    , , & Proc. Natl. Acad. Sci. USA 104, 18946–18951 (2007).

  15. 15.

    , , & Proc. Natl. Acad. Sci. USA 101, 8342–8347 (2004).

  16. 16.

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

  17. 17.

    & Proc. Natl. Acad. Sci. USA 101, 2293–2298 (2004).

  18. 18.

    , & Biochim. Biophys. Acta 1760, 1138–1149 (2006).

  19. 19.

    , , & Bioessays 30, 955–964 (2008).

  20. 20.

    et al. Nature 447, 453–457 (2007).

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.

Author information

Author notes

    • Vytautas Smirnovas
    •  & Gerald S Baron

    These authors contributed equally to this study.

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. Search for Vytautas Smirnovas in:

  2. Search for Gerald S Baron in:

  3. Search for Danielle K Offerdahl in:

  4. Search for Gregory J Raymond in:

  5. Search for Byron Caughey in:

  6. Search for Witold K Surewicz in:

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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Witold K Surewicz.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–4, Supplementary Methods and Supplementary Discussion

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nsmb.2035

Further reading