Yeast prions prion evidence

What is the nature of the insoluble forms of the prion protein They are hard to study because of the extreme insolubility, but the conversion of a helix to (3 sheet seems to be fundamental to the process and has been confirmed for the yeast prion by X-ray diffraction.11 It has been known since the 1950s that many soluble a-helix-rich proteins can be transformed easily into a fibrillar form in which the polypeptide chains are thought to form a P sheet. The chains are probably folded into hairpin loops that form an antiparallel P sheet (see Fig. 2-ll).ii-11 For example, by heating at pH 2 insulin can be converted to fibrils, whose polarized infrared spectrum (Fig. 23-3A) indicates a cross-P structure with strands lying perpendicular to the fibril axis >mm Many other proteins are also able to undergo similar transformation. Most biophysical evidence is consistent with the cross-P structure for the fibrils, which typically have diameters of 7-12 rnn."-11 These may be formed by association of thinner 2 to 5 nm fibrils.00 However, P-helical structures have been proposed for some amyloid fibrils 3 and polyproline II helices for others. 1 11... 

While not all the functions of the verified and putative yeast prions have been established, nevertheless it is already evident that fungal prion proteins are involved in the functioning and/or regulation of several different cellular processes. In particular, a number play important roles in gene regulation, either at the... 

This chapter focuses on recent advances in our understanding of the molecular processes underlying the inheritance and functional consequences of the Saccharomyces cerevisiae prion P.SY+. An expanded discussion of the history of PSI+ including a summary of evidence supporting its classification as a yeast prion can be found in Volume 57 of Advances in Protein Chemistry (Serio and Lindquist, 2001). 

XI. Comparison of the Evidence for Yeast Prions with that for TSEs... 32V... 

Further evidence for the phenomenon of self-propagating protein conformers was provided by the discovery of proteins with prion-like properties in the budding yeast Saccharomyces cerevisiae [41]. The chapter by Mick Tuite [165, 166] in this book will provide a detailed review about fungal prions and their cellular functions. In addition, it has been reported that the translation regulator CPEB from Aplysia can act as a self-sustaining prion-like protein in the nervous system [42—44]. 

Kawai-Noma S, Pack CG, Kojidani T, Asakawa H, Hiraoka Y, Kinjo M, Haraguchi T, Taguchi H, Hirata A (2010) In vivo evidence for the fibrillar structures of Sup35 prions in yeast cells. J Cell Biol 190 223-231... 

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... 

H. E. Sparrer, A, Santoso, F. C. Szoka Jr., J. S. Weissman, Evidence for the prion hypothesis induction of the yeast [PSI + ] factor by in vitro-converted Sup35 protein. Science 2000, 289, 595-599. 

---