Since their original identification, prions have represented enigmatic agents that defy the classical concept of genetic inheritance. For almost four decades, the high-resolution structure of PrPSc, the infectious and misfolded counterpart of the cellular prion protein (PrPC), has remained elusive, mostly due to technical challenges posed by its high insolubility and aggregation propensity. As a result, such a lack of information has critically hampered the search for an effective therapy against prion diseases. Nevertheless, multiple attempts to get insights into the structure of PrPSc have provided important experimental constraints that, despite being at limited resolution, are paving the way for the application of computer-aided technologies to model the three-dimensional architecture of prions and their templated replication mechanism. Here, we review the most relevant studies carried out so far to elucidate the conformation of infectious PrPSc and offer an overview of the most advanced molecular models to explain prion structure and conversion.

Understanding prion structure and conversion / Spagnolli, G.; Requena, J. R.; Biasini, E.. - 175:(2020), pp. 19-30. [10.1016/bs.pmbts.2020.07.005]

Understanding prion structure and conversion

Spagnolli G.;Biasini E.
2020-01-01

Abstract

Since their original identification, prions have represented enigmatic agents that defy the classical concept of genetic inheritance. For almost four decades, the high-resolution structure of PrPSc, the infectious and misfolded counterpart of the cellular prion protein (PrPC), has remained elusive, mostly due to technical challenges posed by its high insolubility and aggregation propensity. As a result, such a lack of information has critically hampered the search for an effective therapy against prion diseases. Nevertheless, multiple attempts to get insights into the structure of PrPSc have provided important experimental constraints that, despite being at limited resolution, are paving the way for the application of computer-aided technologies to model the three-dimensional architecture of prions and their templated replication mechanism. Here, we review the most relevant studies carried out so far to elucidate the conformation of infectious PrPSc and offer an overview of the most advanced molecular models to explain prion structure and conversion.
2020
Progress in Molecular Biology and Translational Science
New York, USA
Elsevier B.V.
9780128200025
Spagnolli, G.; Requena, J. R.; Biasini, E.
Understanding prion structure and conversion / Spagnolli, G.; Requena, J. R.; Biasini, E.. - 175:(2020), pp. 19-30. [10.1016/bs.pmbts.2020.07.005]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/283897
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