Prion amyloids

Diaz-Avalos, R., King, C. Y., Wall,J., Simon, M., and Caspar, D. L. (2005). Strain-specific morphologies of yeast prion amyloid fibrils. Proc. Natl. Acad. Sci. USA 102, 10165-10170. 

Diaz-Avalos, R., King, C. Y., Wall,J., Simon, M., and Caspar, D. L. (2005). Strain-specific morphologies of yeast prion amyloid fibrils. Proc. Natl. Acad. Sci. USA 102,10165-10170. Donne, D. G., Viles, J. H., Groth, D., Mehlhom, I., James, T. L., Cohen, F. E., Prusiner, S. B., Wright, P. E., and Dyson, H.J. (1997). Structure of the recombinant full-length hamster prion protein PrP(29-231) The N terminus is highly flexible. Proc. Natl. Acad. Sci. USA 94, 13452-13457. 

Jones, E. M., and Surewicz, W. K. (2005). Fibril conformation as the basis of species- and strain-dependent seeding specificity of mammalian prion amyloids. Cell 121, 63-72. 

Jones, E. M., and Surewicz, W. K. (2005). Fibril conformation as the basis of species- and strain-dependent seeding specificity of mammalian prion amyloids. Cell 121, 63-72. Kad, N. M., Myers, S. L., Smith, D. P., Smith, D. A., Radford, S. E., and Thomson, N. H. (2003). Hierarchical assembly of beta2-microglobulin amyloid in vitro revealed by atomic force microscopy./. Mol. Biol. 330, 785-797. 

These results indicate that is it possible to change the fold of a protein by changing a restricted set of residues. They also confirm the validity of the rules for stability of helical folds that have been obtained by analysis of experimentally determined protein structures. One obvious impliction of this work is that it might be possible, by just changing a few residues in Janus, to design a mutant that flip-flops between a helical and p sheet structures. Such a polypeptide would be a very interesting model system for prions and other amyloid proteins. 

Come JH, Fraser PE, Lansbury PT, Jr. A kinetic model for amyloid formation in the prion diseases importance of seeding. Proc Natl Acad Sci USA 1993 90 5959-5963. 

Kelly JW (1998) The environmental dependency of protein folding best explains prion and amyloid diseases. Proc Natl Acad Sci USA 95 930-932. 

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. 

Wang H, Duennwald ML, Roberts BE, Rozeboom LM, Zhang YL, Steele AD, Krishnan R, Su LJ, Griffin D, Mukhopadhyay S (2008) Direct and selective elimination of specific prions and amyloids by 4, 5-dianilinophthalimide and analogs. Proc Natl Acad Sci 105... 

Volume 309. Amyloid, Prions, and Other Protein Aggregates Edited by Ronald Wetzel... 

IV. Recent Advances in Structural Studies of Amyloid and Prion Fibrils. 10... 

Fig. 4. New structural models for amyloid and prion filaments with the parallel and in-register arrangement of //-strands in the //-sheets. //-Strands are denoted by arrows. The filaments are formed by hydrogen-bonded stacks of repetitive units. Axial projections of single repetitive units corresponding to each model are shown on the top. Lateral views of the overall structures are on the bottom. (A) The core of a //-helical model of the //-amyloid protofilament (Petkova et al., 2002). Two such protofilaments coil around one another to form a //-amyloid fibril. (B) The core of a //-helical model of the HET-s prion fibril (Ritter et al., 2005). The repetitive unit consists of two //-helical coils. (C) The core of a superpleated //-structura l model suggested for yeast prion Ure2p protofilaments and other amyloids (Kajava et al., 2004).

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