Fungal prions

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Fungal prions have been investigated and lead to a deeper understanding of disease-forming mammilian prions.

Prion-like proteins are found naturally in some plants and non-mammalian animals. Some of these are not associated with any disease state and may possibly even have a useful role. ^[1]. Because of this, scientists reasoned that such proteins could give some sort of evolutionary advantage to their host. This was suggested to be the case in a species of fungus, Podospora anserina. Genetically compatible colonies of this fungus can merge together and share cellular contents such as nutrients and cytoplasm. A natural system of protective "incompatibility" proteins exists to prevent promiscuous sharing between unrelated colonies. One such protein, called HET-S, adopts a prion-like form in order to function properly ^[2]. The prion form of HET-S spreads rapidly throughout the cellular network of a colony and can convert the non-prion form of the protein to a prion state after compatible colonies have merged ^[3]. However, when an incompatible colony tries to merge with a prion-containing colony, the prion causes the "invader" cells to die, ensuring that only related colonies obtain the benefit of sharing resources.

Contents 1 Sup35p & Ure2p 2 Classification 3 References 4 See also

[edit] Sup35p & Ure2p

In 1965, Brian Cox, a geneticist working with the yeast Saccharomyces cerevisiae, described a genetic trait (termed [PSI+]) with an unusual pattern of inheritance. Despite many years of effort, Cox could not identify a conventional mutation that was responsible for the [PSI+] trait. In 1994, yeast geneticist Reed Wickner correctly hypothesized that [PSI+] as well as another mysterious heritable trait, [URE3], resulted from prion forms of certain normal cellular proteins ^[4]. It was soon noticed that heat shock proteins (which help other proteins fold properly) were intimately tied to the inheritance and transmission of [PSI+] and many other yeast prions. Since then, researchers have unravelled how the proteins that code for [PSI+] and [URE3] can convert between prion and non-prion forms, as well as the consequences of having intracellular prions. When exposed to certain adverse conditions, [PSI+] cells actually fare better than their prion-free siblings ^[5]; this finding suggests that, in some proteins, the ability to adopt a prion form may result from positive evolutionary selection ^[6]. It has been speculated that the ability to convert between prion infected and prion-free forms enables yeast to quickly and reversibly adapt in variable environments. Nevertheless, Wickner maintains that [URE3] and [PSI+] are diseases ^[7].

[edit] Classification

Fungal Prions
Protein	Natural Host	Normal Function	Prion State	Prion Phenotype
Ure2p	Saccharomyces cerevisiae	Nitrogen catabolite repressor	[URE3]	Growth on poor nitrogen sources
Sup35p	Saccharomyces cerevisiae	Translation termination factor	[PSI+]	Increased levels of nonsense suppression
Rnq1p	Saccharomyces cerevisiae	Protein template factor	[RNQ+]	Promotes aggregation of other prions
HET-S	Podospora anserina	Regulates heterokaryon incompatabillity	[Het-s]	Heterokaryon formation between incompatible strains

As of 2003, the following proteins in Saccharomyces cerevisiae had been identified or postulated as prions:

• Sup35p, forming the [PSI+] element;
• Ure2p, forming the [URE3] element;
• Rnq1p, forming the [RNQ+] element (also known as [PIN+])
• A fifth prion protein, forming the [ISP+] element remains to be identified.

[edit] References

1. ^ A census of glutamine/asparagine-rich regions: Implications for their conserved function and the prediction of novel prions. PNAS USA. 2000 Oct 24; 97(22): 11910-5 Free text
2. ^ The protein product of the het-s heterokaryon incompatibility gene of the fungus Podospora anserina behaves as a prion analog. PNAS USA. 1997 Sep 2; 94(18): 9773-8 Free text
3. ^ Amyloid aggregates of the HET-S prionprotein are infectious. PNAS USA. 2002 May 28; 99(11): 7402-7 Free text
4. ^ [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science. 1994 Apr 22; 264(5158): 566-9 Abstract
5. ^ A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature. 2000 Sep 28; 407(6803): 477-83 Abstract
6. ^ A small reservoir of disabled ORFs in the yeast genome and its implications for the dynamics of proteome evolution. J Mol Biol. 2002 Feb 22; 316(3): 409-19 Abstract
7. ^ Yeast prions [URE3] and [PSI⁺] are diseases. PNAS USA. 2005 July 26; 102(30): 10575-80 Free text

[edit] See also

• Prion
• Sup35p
• Epigenetics