Prion containment

Masison, D. C., and Wickner, R. B. (1995). Prion-inducing domain of yeast Ure2p and protease resistance of Ure2p in prion-containing cells. Science 270, 93-95. 

Keywords Cervid prions Chronic wasting disease Prion containment Wild-life prion disease Zoonotic potential... 

Vimses are one of the smallest biological entities (except viroids and prions) that carry all the iaformation necessary for thek own reproduction. They are unique, differing from procaryotes and eucaryotes ia that they carry only one type of nucleic acid as genetic material, which can be transported by the vims from one cell to another. Vimses are composed of a shell of proteki enclosing a core of nucleic acid, either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), that codes for vkal reproduction. The outer shell serves as a protective coat to keep the nucleic acid kitact and safe from enzymatic destmction. In addition to thek proteki coat, some vimses contain an outer covering known as an outer envelope. This outer envelope consists of a Hpid or polysaccharide material. 

This chapter has reviewed the application of ROA to studies of unfolded proteins, an area of much current interest central to fundamental protein science and also to practical problems in areas as diverse as medicine and food science. Because the many discrete structure-sensitive bands present in protein ROA spectra, the technique provides a fresh perspective on the structure and behavior of unfolded proteins, and of unfolded sequences in proteins such as A-gliadin and prions which contain distinct structured and unstructured domains. It also provides new insight into the complexity of order in molten globule and reduced protein states, and of the more mobile sequences in fully folded proteins such as /1-lactoglobulin. With the promise of commercial ROA instruments becoming available in the near future, ROA should find many applications in protein science. Since many gene sequences code for natively unfolded proteins in addition to those coding for proteins with well-defined tertiary folds, both of which are equally accessible to ROA studies, ROA should find wide application in structural proteomics. 

In consideration of thermal stability, a calorimetric investigation of Ure2p prion domain-containing filaments detected no evidence of these domains denaturing up to 105°C (Baxa et al., 2004). In comparison, most proteins denature at temperatures of 50—70°C and rarely exceed 80—90°C, except for proteins of extreme thermophiles. 

Cross-/] structure has been demonstrated for Sup35pNM filaments. Serio et al. (2000) observed a 0.47-nm reflection by X-ray diffraction, and subsequently this reflection was shown to be meridional both by X-ray fiber diffraction (Kishimoto et al., 2004) and electron diffraction (King and Diaz-Avalos, 2004). In the Ure2p system, cross-/ structure has been established by electron diffraction from prion domain filaments preserved in vitreous ice (Fig. 7 Baxa et al, 2005). In addition, a 0.47-nm reflection was detected by both X-ray diffraction and electron diffraction from filament preparations of full-length Ure2p and the Ure2p1 65-GFP fusion, indicating that they contain the same structure (Fig. 7 Baxa et al, 2005). 

Recently, a seven-residue peptide from the Sup35p prion domain has been analyzed by X-ray crystallography (Nelson et al., 2005). Although there is, in general, little reason to suppose that a short peptide will assume the same structure in a crystal as it will in the context of a folded protein containing it, these crystals seem to be related to amyloid fibrils of the same... 

Inouye, H., and Kirschner, D. A. (1997). X-ray diffraction analysis of scrapie prion Intermediate and folded structures in a peptide containing two putative alpha-helices./. Mol. Biol. 268, 375-389. 

NMR characterization of the recombinant mouse,hamster, bovine and human prion proteins showed that all these molecules share a common architecture, consisting of a flexible unstructured N-terminal tail of about 100 residues from position 23 to position 124 attached to a globular domain within residues 125-228. The globular domain contains a double-stranded anti-parallel /1-sheet and three ot-helices (Fig. 6). 

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