The prion protein: structural features and related toxic peptides(544 views) Ronga L, Tizzano B, Palladino P, Ragone R, Urso E, Maffia M, Ruvo M, Benedetti E, Rossi F
Chem Biol Drug Des (ISSN: 1747-0277, 1747-0285), 2006 Sep; 68(3): 139-147.
Dipartimento Delle Scienze Biologiche, C.I.R.Pe.B., CNR, Via Mezzocannone 16, 80134 Napoli, Italy
Dipartimento di Biochimica e Biofisica, CRISCEB, Seconda Università di Napoli, Via Costantinopoli 16, 80138 Napoli, Italy
Dipartimento di Scienze e Tecnologie Biologiche Ed Ambientali, Università degli Studi di Lecce, 73100 Lecce, Italy
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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
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The prion protein: structural features and related toxic peptides