Yeast Prions: Their Assembly into Protein Fibrils and the Role of Assembly Modulators - The Functional Fold: Amyloid Structures in Nature - page 95

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allantoate transporter Dal5p. In its functionally compromised form

30

associated to the [URE3] trait, Ure2p is not capable of sequestering

Gln3p in the cytoplasm and the transcription of a number of genes
becomes constitutive. For example, the cells express Dalp5p and
import in a constitutive manner; ureidosuccinate, a precursor
of uracil, only imported by the yeast cells when they are grown
in the absence of simple nitrogen sources such as ammonium or
glutamine.
Ure2p (Swiss-Prot P23202) has a calculated molecular mass of
40.2 kDa and is composed of 354 amino acid residues (Fig. 6.1). The
flexible N-terminal part of Ure2p extending from amino acid residue
1 to 93

31

is very rich in Q, N, S, and T residues (62%). This region
is required for the propagation of the [URE3] phenotype

32

and is
referred to as the PrD of the protein. The C-terminal domain that
extends from amino acid residues 94 to 354

31

complements URE2

gene deletion and therefore constitutes the functional domain of
the protein.

32

It is compactly folded (Fig. 6.1; PDB accession code

33-35 36

1G6Y), binds glutathione (PDB accession code 1JZR), and

exhibits glutathione perroxidase activity.

37

6.3.3 The [Het-s] Trait

The fusion of two different filaments contacting

each other into heterokaryon is tightly regulated and requires,
among other things, that the two filaments are genetically identical
at the

Podospora anserina

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het-s locus. Two common alleles of this locus, called het-s

and , encode cytosolic polypeptides that differ in 13 amino

acid residues out of 289 distributed throughout the protein.

het-S

39

The
protein HET-s exist under two states termed [Het-s*] and [Het-s].
Strains in the [Het-s*] state are indifferent to the status of

their fusion partner. In contrast, an apoptotic reaction occurs leading
to the death of the heterocaryotic cell upon fusion of a filament in its
[Het-s] state with a filament containing the protein HET-S.

het-s / het-S

6

The HET-s
protein (TrEMBL Q03689) has a calculated molecular mass of 32
kDa. It has no remarkable features (Fig. 6.1). The C-terminal domain
of the protein spanning amino acid residues 218-289 is nowadays
considered essential for prion propagation, although the N-terminal
26 amino acid residues and point mutations at amino acid residues
23 and 33 were previously thought to be at one point as critical for
prion propagation.

40,41