The prion protein: structural features and related toxic peptides

Prion diseases are characterized by the conversion of the physiological cellular form of the prion protein (PrPC) into an insoluble, partially protease-resistant abnormal scrapie form (PrPSc). PrPC is normally expressed in mammalian cell and is highly conserved among species, although its role in cellular function remains elusive. The conversion of PrPC to PrPSc 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.

The prion protein: structural features and related toxic peptides

Query:  [X]
Options:	AnyAllExact    Extended      IBB affiliation
	ORAND
Authors:  [X]
Paper type:  [X]
Start date:  [X]
End date:  [X]
Site:	All sitesNaples - De AmicisNaples - CastellinoTurin
	StaffResearch areasActivitiesBibliographyPapersCMSGeneric [Clear form]