Last week we learned about primary structures of proteins: the order of their amino acids. We know that the secondary and tertiary structure of the prion protein causes it to be normal versus infectious, so I was curious about the primary structure of the prion proteins. I assumed it was always the same, but found out via a little research that this is not the case. Sometimes, different amino acids are in different places in the prion. This does not change the overall structure/function of the protein, but it can have smaller effects.
For instance, for Chronic Wasting Disease in deer and elk, there appear to be two strains of prion diseases caused by a variation in the primary structure of the protein. These strains are differentiated by their incubation times and different neuropathological patterns. Apparently the variations that might have caused these differences relate to the difference in residue 226 of the elk prion protein, which can be glutamic acid or glutamine.
Another instance of primary structure affecting prion disease is found in humans, at codon 129 of the human prion protein gene. It can encode for either methionine or valine. This difference can cause changes in how susceptible a human is to sporadic and/or infectious prion diseases. It can also affect the age of onset for prion diseases. These differences may even affect the mechanism and kinetics of the protein unfolding and refolding into the maladaptive form.
It seems that changing a couple amino acids does not affect the overall stability of this protein, but does affect how it unfolds/folds. Differences in the hydrophobic interactions might then affect how the proteins are attracted to each other/interact with each other, leading to the differences in protein aggregation that cause differences in how the disease starts.