Conformations of prion proteins

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

Situations which can change the conformation of prion proteins are related to the activation of microglial cells, releasing proinflammatory cytokines and reactive oxygen species. Hiis elevated oxidative stress may somehow alter the conformation of the protein. Experiments with synthetic human prion peptides (PrP 106-126, PrP 127-147) revealed that the peptide structure is the relevant toxic factor for neuronal cells. PC 12 cells in vitro died... 

Yamamoto N, Kuwata K (2009) Regulating the conformation of prion protein through ligand binding. J Phys Chem B 113 12853... 

J., James, W., Tahiri-Alaoui, A. (2003). Characterization of 2 -fluoro-RNA aptamers that bind preferentially to disease-associated conformations of prion protein and inhibit conversion. J Biol Chem 278, 39697-39705. 

Cohen FE, Prusiner SB (1998) Pathologic conformations of prion proteins. Annu Rev Biochem 67 793-819 Coles M, Bicknell W, Watson AA, FairUe DP, Craik DJ (1998) Solution structure of amyloid beta-peptide(l-40) in a water-micelle environment. Is the membrane-spanning domain where we think it is Biochemistry 37 11064-11077... 

New Approaches Detection Secondary Conformation of Prion Protein in Frozen-Section Tissue by Fourier-Transform Infrared Microscopy... 

Baskakov, I. V., Legname, G., Prusiner, S. B., and Cohen, F. E. (2001). Folding of prion protein to its native a-helical conformation is under kinetic control. J. Biol. Chem. 276, 19687-19690. 

Ragg, E., Tagliavini, F., Malesani, P., Monticelli, L., Bugiani, O., Forloni, G., and Salmona, M. (1999). Determination of solution conformations of PrP106-126, a neurotoxic fragment of prion protein, by 1H NMR and restrained molecular dynamics. Eur.J. Biochem. 266, 1192-1201. 

A hard-to-understand aspect of the "protein-only" theory of prion diseases is the existence of various "strains" of prion proteins. These do not involve differences in amino acid sequence but differences in the conformations of the PrPSc forms and in the glycosylation patterns. dmw How can there be several different conformations of the same protein, all of which seed the conversion of normal PrP into differing insoluble forms In spite of this puzzle, support for the explanation of strain differences comes from a yeast prion system, which involves transcription termination factor eRF3.x z In this system, which involves a prion whose insoluble form can be redissolved by guanidine hydrochloride,aa differing strains have also been described.ybb cc Nevertheless, the presence of the various strains of animal prions, as well as observed vaccination of inbred mice against specific strains,dd may be more readily understood if the disease is transmitted by an unidentified virus rather than by a pure protein.1/U ee/ff In fact, the diseases have not been successfully transmitted by truly virus-free proteins synthesized from recombinant DNA.ee... 

This disease develops when an abnormal prion protein present in the cadaveric material induces a cascade of conformational changes in host protein. Creutzfeldt-Jakob disease in recipients of somatropin differs from the sporadic form, in that it usually presents with cerebellar signs rather than cognitive impairment, and also in the prominence of prion protein amyloid plaques in nervous tissue (18). In a review, 139 cases of Creutzfeldt-Jakob disease were identified worldwide in people treated with cadaveric somatropin before recombinant human growth hormone became available in the mid-1980s (19). The prevalence of this fatal neurodegenerative condition in recipients of somatropin ranges from 0.3% in the USA to 4.4% in France. Creutzfeldt-Jakob disease has been reported to start at 4-30 years after therapy with cadaveric somatropin (18), so that further cases are anticipated and continue to be reported (20). 

EMPs as Carriers of Molecules. In addition to measurable antigens, EMPs as other MPs, are also carriers of molecules. Conformationally changed prion proteins, believed to aid in the propagation of spongiform encephalopathies, have been detected on EMPs released by infected ECs [68]. This finding indicates that EMPs may be active players in the infectious process of spongiform encephalopathies. 

As discussed earlier, conformational change/structural perturbation is a prerequisite for amyloid formation. Exposure to UV light did not initiate the fibril formation it led to amorphous aggregation of prion protein and no observable change to the other two proteins. We have employed conditions that are known to favor amyloid fibril formation and investigated the effect of UV light exposure of these proteins on their ability to form amyloid fibrils. 

Langella E, Improta R, Barone V (2004) Checking the pH-induced conformational transition of prion protein by molecular dynamics simulations effect of protonation of histidine residues. Biophys J 87 3623... 

Chemical biology methods have been utilized in three different aspects of prion protein (PrPc) research. The method was used for the structure determination of PrP and the mechanism of PrP-prion (PrPsc) conversion. Furthermore, the question of infectivity can only be answered unequivocally if PrP preparation are used which have been obtained either by heterologous expression or by chemical synthesis. A further line of experiments was directed to simulate PrP posttransla-tional modifications like attachment of a GPI-anchor or glycosylation. Finally, small medicinally compatible molecules have been used to interfere with the PrP-PrPsc conformational switch. In this review we will address these chemical biology aspects of prion research. 

Sun Y, Breydo L, Makarava N, Yang Q, Bocharova OV, Baskakov IV (2007) Site-specific conformational studies of prion protein (PrP) amyloid fibrils revealed two cooperative folding domains within amyloid structure. J Biol Chem 282 9090-9097... 

SIMULATIONS AND COMPUTATIONAL ANALYSES OF PRION PROTEIN CONFORMATIONS... 

Soto, C., Kascsak, R.J., Saborio, G.P., Aucouturier, P., Wisniewski, T., Prelli, F., Kascsak, R., Mendez, E., Harris, DA., Ironside, J., Tagliavini, F., Carp, R.I., and Frangione, B. (2000). Reversion of prion protein conformational changes by synthetic beta-sheet breaker peptides. Lancet 355, 192-197. 

Jackson, G. S., Hosszu, L. L. R, Power, A., Hill, A. F., Kenney, J., Seiibil, H., Craven, C. J., Waltho, J. R, Qarke, A. R., and Collinge, J. 1999. Reversible conversion of monomeric human prion protein between native emd fibrilogenic conformations. Science 283 1935-1937 Jeffrey, M., Gonzalez, L., Espenes, A., Press, C. M., Martin, S., Chaplin, M., DAvis, L., Landsverk, T., MacAldowie, C., Eaton, S., and McGovern, G. 2006. Transportation of prion protein across the intestineil mucosa of scrapie-susceptible and scrapie-resistant sheep. J. Pathol. 209 4-14... 

Slade, S.E. Thalassinos, K. Hilton, G.R. Pinheiro, T. Blindauer, C.A. Bowers, M.T. Scrivens, 1. Travelling wave ion mobility mass spectrometry-based conformational studies of prion protein - effects of metal cation binding and buffer gas. Proc. 56th ASMS Conference on Mass Spectrometry and Allied Topics, Denver, CO, lune 1-5, 2008, MP 457. 

The detection of secondary conformation in prion protein by Fourier-transformed infrared microscopy is discussed by Norio Miyoshi, Hiroyuki Okada, Masuhiro Takata, Moriichi Shinagawa, and Kenichi Akao. 

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