New insights into structural determinants of prion protein folding and stability |
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Authors: | Federico Benetti Giuseppe Legname |
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Affiliation: | 1.Laboratory of Prion Biology, Department of Neuroscience; Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy;2.Current affiliation: ECSIN-European Center for the Sustainable Impact of Nanotechnology, Veneto Nanotech S.C.p.A., Rovigo, Italy;3.ELETTRA - Sincrotrone Trieste S.C.p.A, AREA Science Park, Basovizza, Trieste, Italy |
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Abstract: | Prions are the etiological agent of fatal neurodegenerative diseases called prion diseases or transmissible spongiform encephalopathies. These maladies can be sporadic, genetic or infectious disorders. Prions are due to post-translational modifications of the cellular prion protein leading to the formation of a β-sheet enriched conformer with altered biochemical properties. The molecular events causing prion formation in sporadic prion diseases are still elusive. Recently, we published a research elucidating the contribution of major structural determinants and environmental factors in prion protein folding and stability. Our study highlighted the crucial role of octarepeats in stabilizing prion protein; the presence of a highly enthalpically stable intermediate state in prion-susceptible species; and the role of disulfide bridge in preserving native fold thus avoiding the misfolding to a β-sheet enriched isoform. Taking advantage from these findings, in this work we present new insights into structural determinants of prion protein folding and stability. |
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Keywords: | prion protein folding stability N-terminal domain octarepeat globular domain intermediate state disulfide bridge |
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