New insights into structural determinants of prion protein folding and stability

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 fo...

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Bibliographic Details
Published in:Prion 2015-03, Vol.9 (2), p.119-124
Main Authors: Benetti, Federico, Legname, Giuseppe
Format: Article
Language:English
Subjects:
Animals
Cattle
disulfide bridge
Disulfides - chemistry
Disulfides - metabolism
Extra View
folding
globular domain
Humans
intermediate state
Mice
Models, Biological
N-terminal domain
octarepeat
prion protein
Prions - chemistry
Prions - metabolism
Protein Folding
Protein Stability
Protein Structure, Tertiary
stability
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Summary: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.
ISSN:1933-6896
1933-690X
DOI:10.1080/19336896.2015.1022023