Fungal Prions: Structure, Function and Propagation

Abstract

Prions are not uniquely associated with rare fatal neurodegenerative diseases in the animal kingdom; prions are also found in fungi and in particular the yeast Saccharomyces cerevisiae. As with animal prions, fungal prions are proteins able to exist in one or more self-propagating alternative conformations, but show little primary sequence relationship with the mammalian prion protein PrP. Rather, fungal prions represent a relatively diverse collection of proteins that participate in key cellular processes such as transcription and translation. Upon switching to their prion form, these proteins can generate stable, sometimes beneficial, changes in the host cell phenotype. Much has already been learnt about prion structure, and propagation and de novo generation of the prion state through studies in yeast and these findings are reviewed here.

Heritable yeast prions have a highly organized three-dimensional architecture with interfiber structures

“…Most of them are hubs of cell regulation, and their prion states have a major impact on cell phenotype (3,4,(9)(10)(11). Many more potential prion proteins have been discovered recently (12).…”

“…The middle region, M, is highly charged and helps maintain the soluble nonprion state. The N-terminal region, N, that is strongly enriched in asparagine and glutamine, is amyloidogenic, and promotes prion formation (5,11,19,20). Importantly, the conformational transitions of Author contributions: H.R.S., S.L., J.T., and A.S.F.…”

Patterns of [PSI+] aggregation allow insights into cellular organization of yeast prion aggregates

“…2A) of all confirmed yeast prions identified to date. [3][4][5][6]20 The exact molecular role of Hsp104 on prion biogenesis, especially in vivo, is still under debate (reviewed in refs. 78, 108, 114 and 115), but it is undoubted that it's function in fiber severing plays an essential role for prion propagation.…”

“…They were explained by slightly different conformations of the prion protein in the prion state and the associated biophysical properties, and cause variation of the phenotype associated with the prion. [19][20][21][22][23][24][25][26][27][28][29][30][31] This review will focus mainly on the [PSI + ] prion as the best studied example and only refer to other yeast prions in some particular examples.…”

Nuclear Poly (A)-Binding Protein and Oculopharyngeal Muscular Dystrophy

“…For examples the aggregated fibers known as curli produced by E. coli is important for cell adhesion (Chapman et. al., 2002); yeast prion Sup35, a translation termination factor (eRF3) forms aggregates (Tuite et. al., 2011 ).…”