Yeast prions chaperones

Several studies since then have supported this suggestion, and now it is widely accepted that conformational change/structural perturbation is a prerequisite for amyloid formation. Structural perturbation involves destabilization of the native state, thus forming nonnative states or partially unfolded intermediates (kinetic or thermodynamic intermediates), which are prone to aggregation. Mild to harsh conditions such as low pH, exposure to elevated temperatures, exposure to hydrophobic surfaces and partial denaturation using urea and guanidinium chloride are used to achieve nonnative states. Stabilizers of intermediate states such as trimethylamine N-oxide (TMAO) are also used for amyloidogenesis. However, natively unfolded proteins, such as a-synuclein, tau protein and yeast prion, require some structural stabilization for the formation of partially folded intermediates that are competent for fibril formation. Conditions for partial structural consolidation include low pH, presence of sodium dodecyl sulfate (SDS), temperature or chemical chaperones. 

Chemoff YO, Lindquist SL, Ono B, Inge-Vechtomov SG, Liebman SW (1995) Role of the chaperone protein Hspl04 in propagation of the yeast prion-like factor [psi+]. Science... 

Hung GC, Masison DC (2006) N-terminal domain of yeast Hspl04 chaperone is dispensable for thermotolerance and prion propagation but necessary for curing prions by Hspl04 overexpression. Genetics 173 611-620... 

Kryndushkin DS, Smirnov VN, Ter-Avanesyan MD, Kushnirov W (2002) Increased expression of Hsp40 chaperones, transcriptional factors, and ribosomal protein Rpp 0 can cure yeast prions. J Biol Chem 277 23702-23708... 

Role of the chaperone protein Hspl04 in propagation of the yeast prion-like... 

Alksne LE, Anthony RA, Liebman SW, Warner JR (1993) An accuracy center in the ribosome conserved over 2 billion years. Proc Natl Acad Sci USA 90 9538-9541 Allen KD, Wegrzyn RD, Chernova TA, Muller S, Newnam GP, Winslett PA, Wittich KB, Wilkinson KD, Chernoff YO (2004) Hsp70 chaperones as modulators of prion life cycle novel effects of Ssa and Ssb on the Saccharomyces cerevisiae prion [PS1+]. Genetics 169 1227-1242 All-Robyn JA, Kelley-Geraghty D, Griffin E, Brown N, Liebman SW (1990) Isolation of omnipotent suppressors in an [eta-t] yeast strain. Genetics 124 505-514... 

Kushnirov VV, Kryndushkin DS, Boguta M, Smirnov VN, Ter-Avanesyan MD (2000) Chaperones that cure yeast artificial [PSI-h] and their prion-specific effects. Curr Biol 10 1443-1446 Lai C-H, Chun HH, N as SA, Mitui M, Gamo KM, Du L, Gatti RA (2004) Correction of ATM gene function by aminoglycoside-induced read-through of premature termination codons. Proc Natl Acad Sci USA 101 15676-15681... 

Keywords Molecular chaperone Podospora anserina Prion Prion propagation Propagons Yeast Saccharomyces cerevisiae)... 

Newnam GP, Wegrzyn RD, Lindquist SL, Chemoff YO (1999) Antagonistic interactions between yeast chaperones Hspl04 and Hsp70 in prion curing. Mol Cell Biol 19 1325-1333... 

Kushnirov VV, Kryndushkin DS, Boguta M, Smirnov VN, Ter-Avanesyan MD (2000) Chaperones that cure yeast artificial [PS/ ] and their prion-specific effects. Curr Biol 10 1443-1446... 

Chemoff YO, Newnarn GP, Kumar J, Allen K, Zink AD (1999) Evidence for a protein mutator in yeast role of the Hsp70-related chaperone ssb in formation, stability, and toxicity of the [PST] prion. Mol Cell Biol 19 8103-8112... 

Moosavi B, Wongwigkam J, Tuite MF (2010) Hsp70/Hsp90 co-chaperones are required for efficient Hspl04-mediated elimination of the yeast PSf1 J prion but not for prion propagation. Yeast 27 167-179... 

This volume, the brainchild of two major figures in protein chemistry, David Eisenberg and Peter Kim, covers our current understanding of these cellular components/machines, with an emphasis on their mechanisms of action. In addition, there is a chapter on protein misfolding in prion disease in a yeast system, with some attention given to the influence of molecular chaperones on that process, and one on a system analysis of response to ER stress. 

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