The yeast prion protein Ure2: Structure, function and folding

Abstract

The Saccharomyces cerevisiae protein Ure2 functions as a regulator of nitrogen metabolism and as a glutathione-dependent peroxidase. Ure2 also has the characteristics of a prion, in that it can undergo a heritable conformational change to an aggregated state; the prion form of Ure2 loses the regulatory function, but the enzymatic function appears to be maintained. A number of factors are found to affect the prion properties of Ure2, including mutation and expression levels of molecular chaperones, and the effect of these factors on structure and stability are being investigated. The relationship between structure, function and folding for the yeast prion Ure2 are discussed.

Moonlighting Proteins in Yeasts

“…Rai et al showed that ure2 mutants have phenotypes similar to those of mutants affected in genes encoding GSTs in S. cerevisiae or Schizosaccharomyces pombe, and they concluded that their results were consistent with a role of Ure2 as a GST (118). Although 1-chloro-2,4-dinitrobenzene is considered an almost universal substrate for those enzymes, a number of them fail to show activity toward it (84), and this is the case for Ure2.…”

“…It has also received much attention due to its relationship with [URE3], a non-Mendelian, nonmitochondrial mutation originally isolated by its effects on nitrogen metabolism in yeast (3). The finding that [URE3] is the prion form of Ure2 (145) has prompted multiple studies to understand the processes that affect prion formation and maintenance (84). The ure2 mutant was generated by Lacroute (83) during a study of genes implicated in the regulation of pyrimidine biosynthesis.…”

Importance of the Hsp70 ATPase Domain in Yeast Prion Propagation

“…Conversion of Ure2p into the infectious prion form causes a proportion or Ure2p to form high molecular weight amyloid aggregates that prevent the protein from carrying out its normal function in regulating nitrogen metabolism. Hence, [URE3] cells are capable of utilizing poor nitrogen sources while [ure-0] cells are not (Taylor and Wickner 2001;Lian et al 2006).…”

Characterization of a Phanerochaete chrysosporium Glutathione Transferase Reveals a Novel Structural and Functional Class with Ligandin Properties

“…Currently, at least seven different classes of cytosolic GSTs have been defined in fungi: MAK16, EFB␥, Ure2p, Omega, S-glutathionyl-(chloro)hydroquinone reductase, GTT, and etherase-like. Although some isoforms from the Ure2p, Omega, S-glutathionyl-(chloro)hydroquinone reductase, and GTT have been characterized in yeast (11)(12)(13), Aspergillus sp. (14,15), and Phanerochaete chrysosporium (9,16), the etherase-like class has never been studied to date.…”