Prion conversion

IV. Filament Formation and Prion Conversion Are Based on Amyloidosis... 

Baxa, U., Speransky, V., Steven, A. C., and Wickner, R. B. (2002). Mechanism of inactivation on prion conversion of the Saccharomyces cerevisiae Ure2 protein. Proc. Natl. Acad. Sci. USA 99, 5253-5260. 

In 2001 Soto and colleagues described a new type of cell-free prion conversion reaction called protein-misfolding cyclic amplification (PMCA) which has greatly improved efficiency, continuity, and sensitivity compared to the initial CFC reactions [11]. In the typical PMCA reaction, crude brain extracts are used as a source of the PrPc which is induced to convert by prions or PrPres in the test sample. Under these conditions, PrPres can be amplified to levels that are detectable... 

Besides this theory, other proteins can act as promotors for the prion conversion reaction. In 1996 chemical reagents were investigated and were shown to affect formation and propagation of PrP. Cellular osmolytes and proteinaceous chaperones were tested in this context (Tatzelt et al., 1996b). Chaperones that can prevent the formation of PrpSc (Fig. 4) might act as powerful tools for the generation of anti-TSE therapeutics. 

Sanghera, N. and Pinheiro, T.J., Binding of prion protein to lipid membranes and implications for prion conversion, J Mol Biol 315 (2002) 1241-1256. 

Prion diseases resulting in encephalopathy can be transmitted between individuals within species (more rarely between species) [26-28], A conformational variant of the normal cellular protein PrPs (PrPc) (protease-sensitive or cellular) is believed to catalyze [29] or nucleate [30-33] conversion to the pathological form, PrPR (protease-resistant). This highly unusual nongenetic mode of transmission of an infectious agent has been strongly debated [29]. The observation of multiple examples of nucleated catalysis of aberrant polymerization of protein subunits has... 

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. 

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. 

Prion propagation involves conversion of PrPc to PrPSc 795... 

All three of these predictions from this minimal model are manifest in the etiology of prion disease an inversely proportional relationship between PrPc expression and prion incubation period in transgenic mice predisposition by relatively subtle mutations in the protein sequence and a requirement for molecular homogeneity between PrPSc and PrPc for efficient prion propagation [4, 5, 20]. It is clear that a full understanding of prion propagation will require knowledge both of the structure of PrPc and PrPSc and of the mechanism of conversion between them. 

Caughey, B. Prion protein conversions insight into mechanisms, TSE transmission barriers and strains. Br. Med. Bull. 66 109-120,2003. 

Jackson, G. S. et al. Reversible conversion of monomeric human prion protein between native and fibrilogenic conformations. Science 283 1935-1937,1999. 

Baskakov, I. V., and Bocharova, O. V. (2005). In vitro conversion of mammalian prion protein into amyloid fibrils displays unusual features. Biochemistry 44, 2339-2348. 

Here, we summarize currently available information on four fungal prions with emphasis on the structural properties and transitions of the proteins involved. It is now clear that their conversion to the prion form is accompanied by a change in their state of aggregation from dispersed (soluble)... 

PSI] is the prion of Sup35p, a translation termination factor (Ter-Avanesyan et al., 1994 Wickner, 1994). Conversion of wild-type yeast cells to the infected state results in reduction of the termination activity and, consequendy, to a nonsense suppression phenotype. This property can be used to detect [PSI] by genetic selection (Fig. 2). Sup35p is an essential gene whose knockout leads to cell death. Therefore, it appears that the [PSI] condition corresponds to only partial inactivation of Sup35p and enough of the normal protein is left to avert cell death. 

Uptain, S. M., Sawicki, G. J., Caughey, B., and Lindquist, S. (2001). Strains of PSI1 are distinguished by their efficiencies of prion-mediated conformational conversion. 

DeMarco, M. L., and Daggett, V. (2004). From conversion to aggregation Protofibril formation of the prion protein. Proc. Natl. Acad. Sci. USA 101, 2293-2298. Diaz-Avalos, R., Long, C., Fontano, E., Balbirnie, M., Grothe, R., Eisenberg, D., and Caspar, D. L. D. (2003). Cross-beta structure of an amyloid-forming peptide studied by electron nano-crystallography. Fibre Diffract. Rev. 11, 79-86. 

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