Location: Produce Safety and Microbiology Research
Title: Oxidized methionine is not a prion-specific covalent modification Authors
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: April 7, 2014
Publication Date: June 14, 2014
Citation: Silva, C.J., Erickson-Beltran, M.L., Dynin, I., Hui, C., Carter, J.M. 2014. Oxidized methionine is not a prion-specific covalent modification [abstract]. Meeting Abstract. Current Topics in Biological Chemistry. Paper No. 230. Technical Abstract: The oxidation of methionine residues in the '-helical region of PrPC has been proposed to be important for prion formation. This proposal has been supported by structural studies, model systems and antibody-based experimental evidence. We developed a sensitive mass spectrometry-based method to study the oxidation of a methionine (213 hamster; 216 sheep and elk) in this region. Our approach does not introduce a significant amount of artifactual oxidation, so it permits us to accurately estimate the amount of oxidized methionine present in a prion. We used this method to analyze prions from four hamster strains (263K, 22AH, 139H, and drowsy), ten field cases of scrapie-infected sheep and ten field cases of CWD-infected elk. Using hamster models, we determined that there was no time-dependent increase in the proportion of oxidized methionine present in PrPSc. In the field cases, older animals had the same proportion of oxidized methionine as did younger animals. In both the field cases and the rodent models, the proportion of oxidized methionine was similar in both PrPC and PrPSc. Next, we examined the role of adjacent amino acids in the oxidation of Met216 in sheep. Our analysis showed that the proportion of MetSO216 was highly dependent upon the amino acid residue at position 218 (Ile218>Val218>thr218). This indicates that sheep and elk PrP is intrinsically more susceptible to oxidation. Even though sheep and elk PrP are inherently more susceptible to oxidation the prions present in naturally infected animals show very little oxidation.