Structural definition is important for the propagation of the yeast [PSI+] prion.

Prions are propagated in Saccharomyces cerevisiae with remarkable efficiency, yet we know little about the structural basis of sequence variations in the prion protein that support or prohibit propagation of the prion conformation. We show that certain single-amino-acid substitutions in the prion protein Sup35 impact negatively on the maintenance of the associated prion-based [PSI(+)] trait by combining in vivo phenotypic analysis with solution NMR structural studies. A clear correlation is observed between mutationally induced conformational differences in one of the oligopeptide repeats (R2) in the N terminus of Sup35 and the relative ability to propagate [PSI(+)].

Probing the role of structural features of mouse PrP in yeast by expression as Sup35-PrP fusions.

The yeast Saccharomyces cerevisiae is a tractable model organism in which both to explore the molecular mechanisms underlying the generation of disease-associated protein misfolding and to map the cellular responses to potentially toxic misfolded proteins. Specific targets have included proteins which in certain disease states form amyloids and lead to neurodegeneration. Such studies are greatly facilitated by the extensive 'toolbox' available to the yeast researcher that provides a range of cell engineering options.

Development of a novel yeast cell-based system for studying the aggregation of Alzheimer's disease-associated Abeta peptides in vivo.

Alzheimer's disease is the most common neurodegenerative disease, affecting approximately 50% of humans by age 85. The disease process is associated with aggregation of the Abeta peptides, short 39-43 residue peptides generated through endoproteolytic cleavage of the Alzheimer's precursor protein. While the process of aggregation of purified Abeta peptides in vitro is beginning to be well understood, little is known about this process in vivo.

The [PSI+] prion of Saccharomyces cerevisiae can be propagated by an Hsp104 orthologue from Candida albicans.

The molecular chaperone Hsp104 is not only a key component of the cellular machinery induced to disassemble aggregated proteins in stressed cells of Saccharomyces cerevisiae but also plays an essential role in the propagation of the [PSI+], [URE3], and [RNQ/PIN+] prions in this organism. Here we demonstrate that the fungal pathogen Candida albicans carries an 899-residue stress-inducible orthologue of Hsp104 (CaHsp104) that shows a high degree of amino acid identity to S. cerevisiae Hsp104 (ScHsp104).

Extent of the mouse t complex and its inversions shown by in situ hybridization.

Probes for loci situated near one end of the proximal (Tcp-1) and distal (Qa-2, 3) inversions of the mouse t complex have been hybridized to chromosomes of mice with and without t complexes and with morphologically distinguishable chromosome 17s. Both the probe for Tcp-1 and that for Qa-2, 3 hybridized to clearly different positions on t and non-t chromosomes, thus making visible the extent of the two inversions. The proximal inversion extends from roughly the junction of bands A1 and A2 to band A3, and the distal inversion from band A3 to band C.