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The prion protein: structural features and related toxic peptides
Author(s) -
Ronga Luisa,
Tizzano Barbara,
Palladino Pasquale,
Ragone Raffaele,
Urso Emanuela,
Maffia Michele,
Ruvo Menotti,
Benedetti Ettore,
Rossi Filomena
Publication year - 2006
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2006.00427.x
Subject(s) - context (archaeology) , beta sheet , scrapie , protein structure , chemistry , prion protein , protein secondary structure , peptide sequence , microbiology and biotechnology , helix (gastropod) , biology , biochemistry , biophysics , medicine , paleontology , ecology , disease , pathology , snail , gene
Prion diseases are characterized by the conversion of the physiological cellular form of the prion protein (PrP C ) into an insoluble, partially protease‐resistant abnormal scrapie form (PrP Sc ). PrP C is normally expressed in mammalian cell and is highly conserved among species, although its role in cellular function remains elusive. The conversion of PrP C to PrP Sc parallels a conformational change of the polypeptide from a predominantly α ‐helical to a highly β ‐sheet secondary structure. The pathogenesis and molecular basis of the consequent nerve cell loss are not understood. Limited structural information is available on aggregate formation by this protein as the possible cause of these diseases and on its toxicity. This brief overview focuses on the large amount of structure‐activity studies based on the prion fragment approach, hinging on peptides derived from the unstructured N‐terminal and globular C‐terminal domains. It is well documented that most of the fragments with regular secondary structure, with the exception of helices 1 and 3, possess a high β ‐sheet propensity and tendency to form β ‐sheet‐like aggregates. In this context, helix 2 plays a crucial role because it is able to adopt both misfolded and partially helical conformation. However, only a few mutants are able to display its intrinsic neurotoxicity.