Prion protein contains 5 amino-terminal octapeptide repeats of PHGGGWGQ. This is thought to include a calcium binding domain via nitrogen atoms in the histidine imidazole side chains and deprotonated amide nitrogens from the 2nd and 3rd glycines in the repeat. The ability to bind calcium is therefore pH dependent. NMR shows Calcium binding results in conformational change at the N-terminus.
For human and Syrian Hamster PrP, two glycosylated sites exist on helices 2 and 3 at Asn181 and Asn197. Murine PrP has glycosylation sites as Asn180 and Asn196. A disulfide bond exists between Cys179 of the second helix and Cys214 of the third helix (human PrPC numbering). The protein attaches to the outer surface of the cell membrane by glycosylphosphatidylinositol anchor at its C-terminal Ser231.
The National Scrapie Plan aims to bread out these scrapie polymorphisms by increasing the frequency of the resistant allele. However, PrP-ARR polymorphisms are susceptible to atypical scrapie so this may prove unfruitful.
[beta]-Sheet Containment by Flanking Prolines: Molecular Dynamic Simulations of the Inhibition of [beta]-Sheet Elongation by Proline Residues in Human Prion Protein
Mar 15, 2007; ABSTRACT Previous molecular dynamic simulations have reported elongation of the existing β-sheet in prion proteins. Detailed...