Parole chiave: Amyloid, Copper Binding Protein, N-Linked Glycoprotein, Prion Structure, Prion Toxicity, Transmissible Spongiform Encephalopathies, Amyloid Protein, Antibiotic Agent, Metal Ion, Polyamine Derivative, Polyanion, Polyene Antibiotic Agent, Polypeptide, Prion Protein, Proteinase, Tetracycline, Tetrapyrrole Derivative, Alpha Helix, Amino Terminal Sequence, Beta Sheet, Carboxy Terminal Sequence, Cell Function, Central Nervous System Disease, Conformational Transition, Copper Metabolism, Drug Protein Binding, Enzyme Inhibition, Human, Mammal Cell, Metal Binding, Neuropathology, Nonhuman, Oxidative Stress, Prion Disease, Protein Domain, Protein Expression, Protein Secondary Structure, Review, Scrapie, Species Conservation, Structure Activity Relation, Amino Acid Sequence, Animals, Models, Molecular, Molecular Sequence Data, Nerve Degeneration, Protein Conformation, Protein Structure, Tertiary, Thermodynamics,
*** IBB - CNR *** Dipartimento delle Scienze Biologiche, Università Federico II di Napoli, Istituto di Biostrutture e Bioimmagini, Via Mezzocannone 16, 80134 Napoli, Italy Dipartimento di Biochimica e Biofisica, CRISCEB, Seconda Università di Napoli, Via Costantinopoli 16, 80138 Napoli, Italy Istituto di Scienze dell'Alimentazione, CNR, 83100 Avellino, Italy
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Ronga, L., Langella, E., Palladino, P., Marasco, D., Tizzano, B., Saviano, M., Pedone, C., Ruvo, M., (2006) Proteins, , in press
The physiological form of the prion protein is normally expressed in mammalian cell and is highly conserved among species, although its role in cellular function remains elusive. Available evidence suggests that this protein is essential for neuronal integrity in the brain, possibly with a role in copper metabolism and cellular response to oxidative stress. In prion diseases, the benign cellular form of the protein is converted into an insoluble, protease-resistant abnormal scrapie form. This conversion parallels a conformational change of the polypeptide from a predominantly a-helical to a highly P-sheet secondary structure. The scrapie form accumulates in the central nervous system of affected individuals, and its protease-resistant core aggregates into amyloid Fibrils outside the cell. The pathogenesis and molecular basis of the nerve cell loss that accompanies this process 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. A large amount of structure-activity studies is based on the prion fragment approach, but the resulting information is often difficult to untangle. This overview focuses on the most relevant structural and functional aspects of the prion-induced conformational disease linked to peptides derived from the unstructured N-terminal and globular C-terminal domains.
38 Records (35 escludendo Abstract e Conferenze). Impact factor totale: 122.536 (116.409 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 127.338 (120.992 escludendo Abstract e Conferenze).