Structural Models for Prion Amyloid Filaments

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. 

This model is a polar cross-/ structure with a left-handed twist that complies with the mass-per-unit-length data moreover, it readily accommodates sequence randomization because like residues are still stacked over like residues, regardless of their order, and sequence permutation does not increase the number of charged residues or prolines which would be most likely to destabilize structures of this kind (Fig. 10). The configuration of strands and turns allows some variation without putting charged residues inside the core structure. We envision that structural variations of this kind offer a plausible explanation for the phenomenon of prion variants, as discussed in Section VIII. 

The /(-helix is a well-authenticated fold, having been observed in more than 20 crystal structures, mostly of secreted bacterial proteins (Jenkins and Pickersgill, 2001 Yoder and Jurnak, 1995 see also Kajava and Steven, this volume). In a /(-helix, the polypeptide chain winds around the molecular axis, each coil consisting of three short /(-strands with connecting turns (Fig. 11). Corresponding strands in successive turns are stacked, generating narrow parallel /(-sheets that are aligned with the 

Sing let /J-helix 1 coil per subunit Doublet /S-hellx 2 colls per subunit Triplet /3-helix 3 coils per subunit 

It has been suggested that the Sup35p filament may be a bundle of four cylindrical //-sheets or nanotubes (Kishimoto et al., 2004). The nanotube is a hypothetical structure (Perutz et al, 2002) whose winding of the polypeptide chain is topologically similar to that of a //-helix but it is round in cross section and water filled whereas //-helices have cross sections with triangular or other shapes and water is largely excluded from their interiors (Kajava and Steven, 2006). The model of Kishimoto et al. envisaged six coils 

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