Proteins prions

Y Levy, OM Becker. Wild-type and mutant prion proteins Insights from energy landscape analysis. In E Katzir, B Solomon, A Taraboulos, eds. Conformational Diseases. In press. 

Prions—protein particles that lack nucleic acid— cause fatal transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, scrapie, and bovine spongiform encephalopathy. Prion diseases involve an altered secondary-tertiary strucmre of a namrally occurring protein, PrPc. When PrPc interacts with its pathologic isoform PrPSc, its conformation is transformed from a predominantly a-helical strucmre to the P-sheet strucmre characteristic of PrPSc. 

Creutzfeldt-Jakob disease (CJD) New variant CJD Gerstmann-Straussler-Scheinker disease Fatal familial insomnia Kuru Prion protein Extracellular deposits... 

Kocisko DA, Priola SA, Raymond GJ, Chesebro B, Lansbury PT Jr, Caughey B. Species specificity in the cell-free conversion of prion protein to protease-resistant forms a model for the scrapie species barrier. Proc Natl Acad USA 1995 92 3923-3927. 

Kellershohn N, Laurent M. Species barrier in prion diseases a kinetic interpretation based on the conformational adaptation of the prion protein. Biochem J 1998 334 539-545. 

Cohen FE, Prusiner SB. Pathologic conformations of prion proteins. Annu... 

Saborio GP, Soto C, Kascsak RJ, Levy E, Kascsak R, Harris DA, Frangione B. Cell-lysate conversion of prion protein into its protease-resistant isoform suggests the participation of a cellular chaperone. Biochem Biophys Res Commun 1999 258 470-475. 

Caughey B, Raymond GJ, Bessen RA. Strain-dependent differences in beta-sheet conformations of abnormal prion protein. J Biol Chem 1998 273 32230-32235. 

Caughey WS, Raymond LD, Horiuchi M, Caughey B. Inhibition of protease-resistant prion protein formation by porphyrins and phthalocya-nines. Proc Natl Acad Sci USA 1998 95 12117-12122. 

The conformational plasticity supported by mobile regions within native proteins, partially denatured protein states such as molten globules, and natively unfolded proteins underlies many of the conformational (protein misfolding) diseases (Carrell and Lomas, 1997 Dobson et al., 2001). Many of these diseases involve amyloid fibril formation, as in amyloidosis from mutant human lysozymes, neurodegenerative diseases such as Parkinson s and Alzheimer s due to the hbrillogenic propensities of a -synuclein and tau, and the prion encephalopathies such as scrapie, BSE, and new variant Creutzfeldt-Jacob disease (CJD) where amyloid fibril formation is triggered by exposure to the amyloid form of the prion protein. In addition, aggregation of serine protease inhibitors such as a j-antitrypsin is responsible for diseases such as emphysema and cirrhosis. 

Yang WC, Schmerr MJ, Jackma R et al (2005) Capillary electrophoresis-based noncompetitive immunoassay for the prion protein using fluorescein-labeled protein A as a fluorescent probe. Anal Chem 77 4489 1494... 

Santuccione, A., Sytnyk, V., Leshchyns ka, I., and Schachner, M. (2005) Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth. J. Cell Biol. 169, 341-354. 

Monte Carlo/simulated annealing (MC/SA) algorithm for sequential assignment in uniformly 13C, 15N-labeled proteins [137]. The two-dimensional (2D) NCACX and NCOCX spectra measured for the fibril samples of full-length Syrian hamster prion protein (residues 23-231) have been analyzed by the MC/SA protocol, from which it has been concluded that the fibril core is formed primarily in the region of residues 173-224 [54]. 

PRNP Prion protein 20pl3 Dominant and Transformation of PrPc into PrP C... 

Palmer, M. S., Dryden, A. J., Hughes, J. T. and Collinge, J. Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease. Nature 352 340-342,1991. 

Berr, C., Richard, F., Dufouil, C., Amant, C., Alperovitch, A. and Amouyel, R Polymorphism of the prion protein is associated with cognitive impairment in the elderly the EVA study. Neurology 51 734-737,1998. 

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