Probing Isoforms of the Prion Protein through Tyrosine Nitration

The prion protein (PrP) has multiple stable isoforms. When PrP misfolds, it aggregates and causes neurological disease and death in mammals. The structure of the non-pathogenic isoform has been determined while the structures of the disease related isoforms are unknown. The nitration labeling patterns of three PrP isoforms with peroxynitrite and tetranitromethane, as detected by mass spectrometry, are reported. Two conserved tyrosine residues (tyrosines 149 and 150) are not labeled by either reagent in the normal cellular form of the prion protein but these residues become reactive after the protein has been converted to one of two aggregated isoforms. Another difference observed is that two other conserved tyrosine residues, 225 and 226, are much less reactive in both aggregated isoforms, while all other tyrosine residues show virtually no isoform specific-labeling. Thus, two regions been identified in which Tyr residues undergo a change in solvent accessibility, which may be due to a conformational change in that region or to inter-subunit packing.

Name thesis:degree_name

Master of Science (MS)

Grantor dc:publisher

University of Montana

Year

2007

Author dc:creator

• Lennon, Christopher William

• prion
• structure

Repository record dc:identifier

https://scholarworks.umt.edu/etd/773

OAI identifier oai:identifier

oai:scholarworks.umt.edu:etd-1792