Detecting differences in prion protein conformation by quantifying methionine oxidation

Authors: Silva, Christopher - Chris; Erickson-Beltran, Melissa

Submitted to: ACS Omega
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/24/2021
Publication Date: 1/7/2022
Citation: Silva, C.J., Erickson-Beltran, M.L. 2022. Detecting differences in prion protein conformation by quantifying methionine oxidation. ACS Omega. 7(3):2649-2660. https://doi.org/10.1021/acsomega.1c04989.
DOI: https://doi.org/10.1021/acsomega.1c04989

Interpretive Summary: The pathogenic character of a prion is defined by its shape, which also defines the chemical environment of its amino acids. These differences influence the reactivity of amino acids, depending on the prion’s shape. The amino acid methionine contains a sulfur atom that is vulnerable to oxidation. Cells convert oxidized methionines back to their unoxidized form. Chemical oxidation of methionines can identify methionines on the surface of a prion. This would reveal conformation-dependent information. We identified a set of methionine-containing peptides derived from recombinant PrP (rPrP) and the Sc237 strain hamster-adapted scrapie. We developed a multiple reaction monitoring method (MRM) based method of analyzing the extent of the methionine oxidation in those peptides. This approach can be used define a prion’s conformation and to distinguish among prion strains. The ability to distinguish among the prion conformations is an important component of food safety.

Technical Abstract: A prion's pathogenic character is enciphered in its conformation, which also defines the chemical environments of its amino acids. Differences in chemical environments influence the reactivity of amino acid side chains, in a conformationdependent manner. Chemical oxidation of susceptible methionines would identify those methionines on the surface of a prion, which would reveal conformation-dependent information. We identified a set of methionine-containing peptides derived from the tryptic, chymotryptic, or tryptic/chymotryptic digestion of recombinant prion protein and the Sc237 strain of hamster-adapted scrapie. We developed a multiple reaction monitoring-based method of quantifying the extent of the methionine oxidation in those peptides. This approach can be used to define a prion's conformation and to distinguish among prion strains, which is an important component of food safety.