Re: Why is prion structure so hard to analyze?

Hi Logan,

To answer your first question: prion proteins have been analyzed using X- ray crystallography. Follow this link to the Protein Data Bank and try a search for "prion".
Most of these structures are fragments of PrP or mutant forms of the protein. A problem with the disease-related form of prion protein is that it aggregates into fibrils. These lack the ordered structure required to form crystals (for X-ray diffraction) and are also large/insoluble (a problem for the other commonly-used method in structural biology, NMR spectroscopy).

Second question, about protease resistance: again, it depends on the form of the prion protein. The infectious, mis-folded form is protease-resistant, to a degree that depends on the precise nature of the mutation and the misfolding.

This Wikipedia article is a good basic introduction to prion protein and should be more up to date than the older posts in the MadSci archives.
Hope that helps with your questions,
Neil