Prions Research Today is a free monthly online journal that collates and summarizes the latest research about Prions, including details on mad cow disease, scrapie, cjd.

Relative and regional stabilities of the hamster, mouse, rabbit, and bovine prion proteins toward urea unfolding assessed by nuclear magnetic resonance and circular dichroism spectroscopies.

Julien O, Chatterjee S, Bjorndahl TC, Sweeting B, Acharya S, Semenchenko V, Chakrabartty A, Pai EF, Wishart DS, Sykes BD, Cashman NR

Department of Biochemistry, University of Alberta, Edmonton, AB, Canada T6G 2H7.

The residue-specific urea-induced unfolding patterns of recombinant prion proteins from different species (bovine, rabbit, mouse, and Syrian hamster) were monitored using high-resolution (1)H nuclear magnetic resonance (NMR) spectroscopy. Protein constructs of different lengths, and with and without a His tag attached at the N-terminus, were studied. The various species showed different overall sensitivities toward urea denaturation with stabilities in the following order: hamster ≤ mouse < rabbit < bovine protein. This order is in agreement with recent circular dichroism (CD) spectroscopic measurements for several species [Khan, M. Q. (2010) Proc. Natl. Acad. Sci. U.S.A.107, 19808-19813] and for the bovine protein presented herein. The [urea](1/2) values determined by CD spectroscopy parallel those of the most stable residues observed by NMR spectroscopy. Neither the longer constructs containing an additional hydrophobic region nor the His tag influenced the stability of the structured domain of the constructs studied. The effect of the S174N mutation in rabbit PrP(C) was also investigated. The rank order of the regional stabilities within each protein remained the same for all species. In particular, the residues in the β-sheet region in all four species were more sensitive to urea-induced unfolding than residues in the α2 and α3 helical regions. These observations indicate that the regional specific unfolding pattern is the same for the four mammalian prion proteins studied but militate against the idea that PrP(Sc) formation is linked with the global stability of PrP(C).

Published 30 August 2011 in Biochemistry, 50(35): 7536-45.
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Articles on Prions published 29 August 2011:

Molecular cloning and polymorphism analysis of the prion protein gene in Tan sheep of Ningxia, China.   Gene, 485(2): 102-5.

The resistance or susceptibility of sheep to scrapie is associated with polymorphisms of the prion protein gene (PRNP), particularly, single nucleotide polymorphisms (SNPs) in amino acid positions 136, 154 and 171. The prion protein (PrP) gene sequence and the deduced amino acid alignment of prion protein in Tan sheep, a local Chinese sheep breed traditionally raised in Ningxia, northwestern China, were determined and variability of the PrP amino acids sequence was analyzed in this study. The ... [Abstract] [Full-text]

Articles on Prions published 22 August 2011:

Hierarchical organization in the amyloid core of yeast prion protein Ure2.   J Biol Chem, 286(34): 29691-9.

Formation of amyloid fibrils is involved in a range of fatal human disorders including Alzheimer, Parkinson, and prion diseases. Yeast prions, despite differences in sequence from their mammalian counterparts, share similar features with mammalian prions including infectivity, prion strain phenomenon, and species barrier and thus are good model systems for human prion diseases. Yeast prions normally have long prion domains that presumably form multiple β strands in the fibril, and structural ... [Abstract] [Full-text]

Articles on Prions published 16 August 2011:

Seeding specificity and ultrastructural characteristics of infectious recombinant prions.   Biochemistry, 50(33): 7111-6.

Infectious mouse prions can be produced from a mixture of bacterially expressed recombinant prion protein (recPrP), palmitoyloleoylphosphatidylglycerol (POPG), and RNA [Wang, F.; et al. (2010) Science 327, 1132]. In contrast, amyloid fibers produced from pure recPrP without POPG or RNA (recPrP fibers) fail to infect wild type mice [Colby, D.W.; et al. (2010) PLoS Pathog. 387, e1000736]. We compared the seeding specificity and ultrastructural features of infectious recombinant prions ... [Abstract] [Full-text]

Articles on Prions published 15 August 2011:

Dynamics of polymerization shed light on the mechanisms that lead to multiple amyloid structures of the prion protein.   Biochim Biophys Acta, 1814(10): 1305-17.

It is generally accepted that spongiform encephalopathies result from the aggregation into amyloid of a ubiquitous protein, the so-called prion protein. As a consequence, the dynamics of amyloid formation should explain the characteristics of the prion diseases: infectivity as well as sporadic and genetic occurrence, long incubation time, species barriers and strain specificities. The success of this amyloid hypothesis is due to the good qualitative agreement of this hypothesis with the ... [Abstract] [Full-text]

The extracellular regulated kinase-1 (ERK1) controls regulated alpha-secretase-mediated processing, promoter transactivation, and mRNA levels of the cellular prion protein.   J Biol Chem, 286(33): 29192-206.

The α-secretases A disintegrin and metalloprotease 10 (ADAM10) and ADAM17 trigger constitutive and regulated processing of the cellular prion protein (PrP(c)) yielding N1 fragment. The latter depends on protein kinase C (PKC)-coupled M1/M3 muscarinic receptor activation and subsequent phosphorylation of ADAM17 on its intracytoplasmic threonine 735. Here we show that regulated PrP(c) processing and ADAM17 phosphorylation and activation are controlled by the extracellular-regulated ... [Abstract] [Full-text]

Articles on Prions published 10 August 2011:

Experience with preventive genetic testing of corneal donors in slovakia.   Cornea, 30(9): 987-90.

[Abstract] [Full-text]

Articles on Prions published 9 August 2011:

Steric zipper formed by hydrophobic peptide fragment of Syrian hamster prion protein.   Biochemistry, 50(32): 6815-23.

Steric zippers, where the residues of two neighboring β-sheet layers are tightly interdigitated, have been proposed as fundamental structural units of amyloid fibrils by Eisenberg and co-workers. The steric zipper formed by polypeptides containing the palindromic sequence AGAAAAGA has a distinctive feature that the distance between two interdigitated β-sheet layers is comparable to the interstrand distance of the individual β-sheet. This structural motif is of great interest in the study of ... [Abstract] [Full-text]

In vivo comparison of chronic wasting disease infectivity from deer with variation at prion protein residue 96.   J Virol, 85(17): 9235-8.

Chronic wasting disease (CWD) is a prion disease of cervids that causes neurodegeneration and death. Susceptibility to prion infections, including CWD, can be dependent on the amino acid sequence of the host prion protein (PrP). Here, CWD agent obtained from a deer expressing the 96SS genotype, associated with partial resistance to CWD, was used to infect transgenic (tg) mice expressing either 96GG or 96SS deer PrP. Transgenic mice expressing 96GG deer PrP succumbed to this agent, but tg mice ... [Abstract] [Full-text]

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