Mammalian prion

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. 

Table II compares some basic properties of the fungal prions and the mammalian prion, bringing out similarities and differences between them.

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. 

Westaway, D. Carlson, G.A. (2002) Mammalian prion proteins enigma, variation and vaccination. Trends Biochem. Sci. 27, 301-307. 

Legname G, Baskakov IV, Nguyen HO, Riesner D, Cohen EE, DeArmond SJ, Pi usiiier SB (2004) Syndiedc mammalian prions. Science 305 673-676. 

Generation of Prion Infectivity In Vitro and Synthetic Mammalian Prions. 155... 

The PK-resistance of PrPSc is an easily measurable operational parameter that has played a fundamentally important role in the evolution of concepts regarding the nature of mammalian prions. However, from the perspective of structural biology, this parameter is merely a surrogate of structural information, as PK-resistance may be associated with different structural motifs, and may also result from the presence of additional molecules that associate with PrPSc and prevent access of the protease to potential cleavage sites. 

Early efforts to recapitulate PrPSc formation and mammalian prion propagation in vitro included cell-free conversion reactions in which PrPc was incubated in the presence of PrPSc from TSE-affected animals [85, 172], Such simple incubation resulted in species- and strain-specific conversion of substrate PrPc to a PrPSc-like conformation (as judged by very similar PK resistance) [172], The yields of these conversion reactions were, however, very low, typically substoichiometric with respect to the input PrPSc template. Furthermore, no infectivity could be attributed to the newly converted material [173], indicating that not every PK resistant form of the prion protein is necessarily associated with prion infectivity. 

Zahn R (2003) The octapeptide repeats in mammalian prion protein constitute a pH-dependent folding and aggregation site. J Mol Biol 334 477 -88... 

Smirnovas V, Baron GS, Offerdahl DK et al (2011) Structural organization of brain-derived mammalian prions examined by hydrogen-deuterium exchange. Nat Stmct Mol Biol 18 504-506... 

Bocharova OV, Breydo L, Parfenov AS et al (2005) In vitro conversion of full-length mammalian prion protein produces amyloid form with physical properties of PrP(Sc). J Mol Biol 346 645-659... 

Vanik DL, Surewicz KA, Surewicz WK (2004) Molecular basis of barriers for interspecies transmissibility of mammalian prions. Mol Cell 14 139-145... 

Colby DW, Giles K, Legname G et al (2009) Design and construction of diverse mammalian prion strains. Proc Natl Acad Sci USA 106 20417-20422... 

Kim J, Cali I, Surewicz K et al (2010) Mammalian prions generated from bacterially expressed prion protein in the absence of any mammalian cofactors. J Biol Chem 285 14083-14087... 

One remarkable property of yeast prions and their mammalian counterparts is the ability to take up several different yet stable [PRION+] forms that reflect different but stable conformational states of the prion protein. In the case of mammalian prions these are referred to as prion strains and can result in very distinct neuropathologies [94]. In yeast, however, to avoid confusion with the use of the term strain, which is typically used to describe different lineages of this organism, they are referred to as yeast prion variants . Like mammalian prion strains, yeast prion variants can give rise to variant-specific differences in the [PRION+] phenotypes. 

Studies with mammalian prion PrP have failed to identify any cellular factor, be it a protein, a co-factor or a nucleic acid species that is essential for the generation or propagation of PrPSc. This has led to the assertion that mammalian prions are self-replicating . Fungal prions are however different they require one or more cellular proteins in order to propagate successfully the prion form in vivo. This difference reflects in part the requirement to propagate yeast prions in a matter of... 

Aguzzi, A. and Polymenidou, M. (2004) Mammalian Prion Biology One century of evolving concepts. Cell 116 313-327. 

For structural studies of PrP, recombinant proteins were expressed in Escherichia coli. The constructs used contain either the intact polypeptide chain of the mature form of natural PrP (Fig. 1), possibly with some additional, construct-related residues at either chain end, or fragments thereof. Presently it appears impractical to envisage three-dimensional structure determinations with mammalian prion proteins from natural sources. However, sufficient amounts of natural PrP have been isolated to enable qualitative comparative studies with the recombinant protein by optical spectroscopy. Overall, these experiments indicate close similarity between the natural and the corresponding recombinant prion protein. Thus, the circular dichroism (CD) spectrum of monomeric hamster PrP extracted from hamster brains into a micellar environment of 30 mM w-octyl-P-glucopyranoside at pH 7.5 is typical for... 

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