A second paper on the atomic details of the refined structure has been submitted to Nature Structural Biology. Cohen also have NMR structure close to publication, possibly showing a larger fragment. Warwicker's model is of a normal conformer dimer. However, the necessary transition from helix to sheet in the disease state has an interesting connection with recent observations on the chameleon nature of helix 1 and 2 made by MF Perutz in 27 Feb 97 Nature. With prion protein, a shift in the region 104-122 from helix to sheet is widely taken as the structural correlate of the shift from normal to disease conformer.
Short helices are of course intrinsically less stable because of fewer applicable hydrogen bonds.
Whence Perutz' suggestion for cameleon domains. This fits well with the pre-chameleon suggestion of Glockshuber and Wuthrich that the small original beta sheet nucleates prion structural conversion. Certainly, the quaternary structure has a modulating influence on each monomer. That is, the two conformers are integral to normal prion function. Perutz also reviewed the general case of amyloid-forming proteins, including prions, in the same note.