title: The prion protein: Structural features and related toxic peptides.
abstract: 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 alpha-helical to a highly beta-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 beta-sheet propensity and tendency to form beta-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.
authors.affiliation: Dipartimento delle Scienze Biologiche, C I R Pe B, Università Federico II di Napoli and Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ronga
authors.forename: Barbara
authors.initials: B
authors.lastname: Tizzano
authors.forename: Pasquale
authors.initials: P
authors.lastname: Palladino
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ragone
authors.forename: Emanuela
authors.initials: E
authors.lastname: Urso
authors.forename: Michele
authors.initials: M
authors.lastname: Maffia
authors.forename: Menotti
authors.initials: M
authors.lastname: Ruvo
authors.forename: Ettore
authors.initials: E
authors.lastname: Benedetti
authors.forename: Filomena
authors.initials: F
authors.lastname: Rossi
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D011328:Prions / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D010455:Peptides; D011328:Prions