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Biomolecular NMR Assignments

, Volume 11, Issue 1, pp 75–80 | Cite as

13C and 15N chemical shift assignments of mammalian Y145Stop prion protein amyloid fibrils

  • Theint Theint
  • Philippe S. Nadaud
  • Krystyna Surewicz
  • Witold K. Surewicz
  • Christopher P. JaroniecEmail author
Article

Abstract

The Y145Stop prion protein (PrP23-144), which has been linked to the development of a heritable prionopathy in humans, is a valuable in vitro model for elucidating the structural and molecular basis of amyloid seeding specificities. Here we report the sequential backbone and side-chain 13C and 15N assignments of mouse and Syrian hamster PrP23-144 amyloid fibrils determined by using 2D and 3D magic-angle spinning solid-state NMR. The assigned chemical shifts were used to predict the secondary structures for the core regions of the mouse and Syrian hamster PrP23-144 amyloids, and the results compared to those for human PrP23-144 amyloid, which has previously been analyzed by solid-state NMR techniques.

Keywords

Prion protein Amyloid Magic-angle spinning Solid-state NMR 

Notes

Acknowledgements

This research was supported by NIH (Grants R01GM094357 and S10OD012303 to C.P.J. and P01AI106705 and R01NS083687 to W.K.S.) and the Camille & Henry Dreyfus Foundation (Camille Dreyfus Teacher-Scholar Award to C.P.J.).

References

  1. Aguzzi A, Polymenidou M (2004) Mammalian prion biology: one century of evolving concepts. Cell 116:313–327CrossRefGoogle Scholar
  2. Aguzzi A, Sigurdson C, Heikenwaelder M (2008) Molecular mechanisms of prion pathogenesis. Annu Rev Pathol 3:11–40CrossRefGoogle Scholar
  3. Caughey B, Chesebro B (2001) Transmissible spongiform encephalopathies and prion protein interconversions. Adv Virus Res 56:277–311CrossRefGoogle Scholar
  4. Choi JK, Cali I, Surewicz K, Kong Q, Gambetti P, Surewicz WK (2016) Amyloid fibrils from the N-terminal prion protein fragment are infectious. Proc Natl Acad Sci USA 113:13851–13856CrossRefGoogle Scholar
  5. Cobb NJ, Surewicz WK (2009) Prion diseases and their biochemical mechanisms. BioChemistry 48:2574–2585CrossRefGoogle Scholar
  6. Collinge J (2001) Prion diseases of humans and animals: Their causes and molecular basis. Annu Rev Neurosci 24:519–550CrossRefGoogle Scholar
  7. Collinge J, Clarke AR (2007) A general model of prion strains and their pathogenicity. Science 318:930–936ADSCrossRefGoogle Scholar
  8. Delaglio F, Grzesiek S, Vuister GW, Zhu G, Pfeifer J, Bax A (1995) NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR 6:277–293CrossRefGoogle Scholar
  9. Ghetti B, Piccardo P, Spillantini MG, Ichimiya Y, Porro M, Perini F, Kitamoto T, Tateishi J, Seiler C, Frangione B, Bugiani O, Giaccone G, Prelli F, Goedert M, Dlouhy SR, Tagliavini F (1996) Vascular variant of prion protein cerebral amyloidosis with τ-positive neurofibrillary tangles: The phenotype of the stop codon 145 mutation in PRNP. Proc Natl Acad Sci USA 93:744–748ADSCrossRefGoogle Scholar
  10. Goddard TD, Kneller DG (2006) SPARKY 3. University of California, San FranciscoGoogle Scholar
  11. Helmus JJ, Jaroniec CP (2013) Nmrglue: an open source Python package for the analysis of multidimensional NMR data. J Biomol NMR 55:355–367CrossRefGoogle Scholar
  12. Helmus JJ, Surewicz K, Nadaud PS, Surewicz WK, Jaroniec CP (2008) Molecular conformation and dynamics of the Y145Stop variant of human prion protein in amyloid fibrils. Proc Natl Acad Sci USA 105:6284–6289ADSCrossRefGoogle Scholar
  13. Helmus JJ, Surewicz K, Surewicz WK, Jaroniec CP (2010) Conformational flexibility of Y145Stop human prion protein amyloid fibrils probed by solid-state nuclear magnetic resonance spectroscopy. J Am Chem Soc 132:2393–2403CrossRefGoogle Scholar
  14. Helmus JJ, Surewicz K, Apostol MI, Surewicz WK, Jaroniec CP (2011) Intermolecular alignment in Y145Stop human prion protein amyloid fibrils probed by solid-state NMR spectroscopy. J Am Chem Soc 133:13934–13937CrossRefGoogle Scholar
  15. Jones EM, Surewicz WK (2005) Fibril conformation as the basis of species- and strain-dependent seeding specificity of mammalian prion amyloids. Cell 121:63–72CrossRefGoogle Scholar
  16. Jones EM, Wu B, Surewicz K, Nadaud PS, Helmus JJ, Chen S, Jaroniec CP, Surewicz WK (2011) Structural polymorphism in amyloids: New insights from studies with Y145Stop prion protein fibrils. J Biol Chem 286:42777–42784CrossRefGoogle Scholar
  17. Kundu B, Maiti NR, Jones EM, Surewicz KA, Vanik DL, Surewicz WK (2003) Nucleation-dependent conformational conversion of the Y145Stop variant of human prion protein: Structural clues for prion propagation. Proc Natl Acad Sci USA 100:12069–12074ADSCrossRefGoogle Scholar
  18. Morillas M, Swietnicki W, Gambetti P, Surewicz WK (1999) Membrane environment alters the conformational structure of the recombinant prion protein. J Biol Chem 274:36859–36865CrossRefGoogle Scholar
  19. Prusiner SB (1998) Prions. Proc Natl Acad Sci USA 95:13363–13383ADSCrossRefGoogle Scholar
  20. Sejvar JJ, Schonberger LB, Belay ED (2008) Transmissible spongiform encephalopathies. J Am Vet Med Assoc 233:1705–1712CrossRefGoogle Scholar
  21. Shen Y, Bax A (2013) Protein backbone and sidechain torsion angles predicted from NMR chemical shifts using artificial neural networks. J Biomol NMR 56:227–241CrossRefGoogle Scholar
  22. Surewicz WK, Jones EM, Apetri AC (2006) The emerging principles of mammalian prion propagation and transmissibility barriers: Insight from studies in vitro. Acc Chem Res 39:654–662CrossRefGoogle Scholar
  23. Vanik DL, Surewicz KA, Surewicz WK (2004) Molecular basis of barriers for interspecies transmissibility of mammalian prions. Mol Cell 14:139–145CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.Department of Chemistry and BiochemistryThe Ohio State UniversityColumbusUSA
  2. 2.Department of Physiology and BiophysicsCase Western Reserve UniversityClevelandUSA

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