Prions fungal

STRUCTURE, FUNCTION, AND AMYLOIDOGENESIS OF FUNGAL PRIONS FILAMENT POLYMORPHISM AND PRION VARIANTS... 

C. Relationship of Fungal Prions to Mammalian (Neurotoxic) Prions... 132... 

Here, we summarize currently available information on four fungal prions with emphasis on the structural properties and transitions of the proteins involved. It is now clear that their conversion to the prion form is accompanied by a change in their state of aggregation from dispersed (soluble)... 

Table II compares some basic properties of the fungal prions and the mammalian prion, bringing out similarities and differences between them.

Prions follow a similar route. All fungal prions can be transferred between cells by cytoplasmic mixing as has been confirmed by experiments with cells that have a mutation preventing the fusion of nuclei during mating (=cytoduction) (Ridley et al., 1984). 

Infection by PrPSc is a more challenging—and obscure—process. Pathogens in mammals not only have to spread within an infected organism but also they must spread from one organism to another. The route of transmission followed by PrPSc is more complicated than that of fungal prions and places more requirements on this system. Tissues other than brain are also involved (Aguzzi, 2003 Seeger et al., 2005). 

All fungal prion proteins have a so-called prion domain and a functional domain. The prion domain is a region of the polypeptide chain that is necessary and sufficient for prion formation and maintenance (Fig. 1 Wickner et al., 2002). For Ure2p and Sup35p, the functional domain is responsible for the cellular activity of the normal form of the protein. 

In infected cells, fungal prion proteins are aggregated. This property has been demonstrated in experiments in which the prion protein was fused with green fluorescent protein (GFP). In wild-type cells, fluorescence was homogeneously distributed throughout the cytoplasm while in cells exhibiting the prion phenotype, it was concentrated in discrete spots and/or variably shaped aggregates (Fig. 4 Coustou-Linares et al, 2001 ... 

All fungal prion proteins readily form filaments in vitro (Dos Reis et al., 2002 Glover et al., 1997 Sondheimer and Lindquist, 2000 Taylor et al., 1999). In near-native buffer conditions, filament formation typically occurs in hours to days. Ure2p filaments assembled in vitro have a diameter of —20 nm and like the filaments observed in situ (Section III.A Fig. 4), they are not hollow. 

As noted above, many natively unfolded proteins become folded in the presence of an appropriate interaction partner. Fungal prion domains subscribe to this paradigm whereby the partner is itself (each other) and the interaction represents homotypic polymerization into amyloid. 

In this section, we discuss several recent proposals for how the proteins are arranged in amyloid filaments of fungal prion proteins in light of current experimental data. 

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