Prion proteins, conversion folding

What is the nature of the insoluble forms of the prion protein They are hard to study because of the extreme insolubility, but the conversion of a helix to (3 sheet seems to be fundamental to the process and has been confirmed for the yeast prion by X-ray diffraction.11 It has been known since the 1950s that many soluble a-helix-rich proteins can be transformed easily into a fibrillar form in which the polypeptide chains are thought to form a P sheet. The chains are probably folded into hairpin loops that form an antiparallel P sheet (see Fig. 2-ll).ii-11 For example, by heating at pH 2 insulin can be converted to fibrils, whose polarized infrared spectrum (Fig. 23-3A) indicates a cross-P structure with strands lying perpendicular to the fibril axis >mm Many other proteins are also able to undergo similar transformation. Most biophysical evidence is consistent with the cross-P structure for the fibrils, which typically have diameters of 7-12 rnn."-11 These may be formed by association of thinner 2 to 5 nm fibrils.00 However, P-helical structures have been proposed for some amyloid fibrils 3 and polyproline II helices for others. 1 11... 

Colombo G, Meli M, Morra G, Gabizon R, Gasset M (2009) Methionine sulfoxides on prion protein helix-3 switch on the alpha-fold destabilization required for conversion. PLoS ONE 4 e4296... 

The protein-only hypothesis indicates that the scrapie form of the prion protein can promote the conversion of the cellular form. This leads to the conclusion that prions themselves can act as chaperones (Liautard, 1991). Thermokinetic analysis of protein folding shows that a misfolded chaperone gives rise to new misfolded chaperones, which fit very well to the protein-only hypothesis in which PrP triggers the formation of PrP. ... 

F. Ding, J. J. LaRoeque, and N. V. Dokholyan,/. Biol. Chem., 280, 40235 (2005). Direct Observation of Protein Folding, Aggregation, and a Prion-Like Conformational Conversion. 

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