FC0029
Sup35  -  Sup35 prion amyloid

Biological function
The [PSI⁺] prion of Saccharomyces cerevisiae is an infectious amyloid form of Sup35.

Biochemical evidence
The sequence of the Sup35 prion domain can be randomized without blocking prion formation. Indeed, a single shuffled sequence could give rise to several prion variants. These results suggest that [PSI⁺] formation is driven primarily by the amino acid composition of the Sup35 prion domain, and that the Sup35 oligopeptide repeats are not required for prion maintenance.

Structure/Mechanism
The Q/N content is 46%. The oligopeptide repeat region is not sufficient for aggregation despite its length and high Q/N content; other sequence composition features such as the high number of prolines may preclude aggregation. Presumably there is some set of criteria that an amyloid structure must meet to be stable, such as the need to place charged residues and prolines either on turns or outside the core amyloid structure. If the requirement for a stable prion were rather general such as, for example, a Q/N-rich domain containing at least one stretch of ~20 residues without any prolines or charged residues, then most scrambled versions of the Sup35 PD (with 9.6% charged/proline residues) would be able to form prions. However, in most cases a single properly placed charged residue could disrupt this ability. Maintaining the ability to be a prion and form amyloid after scrambling is suggestive of parallel β -sheet structure.

Mechanism category
tethering

Significance
Fuzziness could make the prion domain easily accessible and amenable for prion formation. Fuzziness also allow alternative pattern of hydrogen bonding interactions between the β-strands. Fuzzy regions outside the prion core also contribute to propagation of the fibers by a yet uncovered mechanism.