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ARS Home » Pacific West Area » Albany, California » Western Regional Research Center » Produce Safety and Microbiology Research » Research » Publications at this Location » Publication #335359
Title: Using mass spectrometry and small molecule reagents to detect distinctive structural features of different prion conformations (strains)

Author
item Silva, Christopher - Chris
item Erickson-Beltran, Melissa
item Dynin, Irina

Submitted to: American Chemical Society National Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 12/22/2016
Publication Date: 4/6/2017
Citation: Silva, C.J., Erickson-Beltran, M.L., Dynin, I.A. 2017. Using mass spectrometry and small molecule reagents to detect distinctive structural features of different prion conformations (strains). Abstracts of the Papers of the American Chemical Society. 253:438-ANYL.

Interpretive Summary:

Technical Abstract: A prion (PrPSc) is a conformer of a normal cellular prion protein (PrPC). Although they are isosequential, PrPSc is an infectious protein able to convert PrPC into the prion conformation and thereby propagate an infection. PrPC is monomeric while PrPSc is a multimer. PrPSc can adopt more than one conformation, which means that a given species can be infected by more than one kind or strain of isosequential prion. For example, hamsters can be infected with five different strains of hamster-adapted scrapie, Sc237 (=263K), drowsy, 139H, 22AH, and 22CH. These five strains were separately isolated from prion-infected hamsters and each was reacted with five different concentrations (0, 1, 5, 10, or 20 mM) of a small molecule reagent that acetylates lysines (N-hydroxysuccinimide ester of acetic acid (Ac-NHS)). Recombinant PrP, derived from bacterial cultures, was used as a control. A multiple reaction monitoring-based mass spectrometry method was used to quantitate the extent of lysine acetylation. The lysines in rPrP react similarly, which indicates that they are equally accessible to the reagent. The lysines present in PrPSc react differently, which indicates that they are differentially exposed to the reagent, which is not surprising, since the chemical environment of an amino acid is determined by the conformation of the protein. Unlike other models, a recently proposed model posits that a prion monomer is a '-solenoid consisting of four beta-sheets joined by loops and turns of amino acids. Prion strains may arise from variations in the register of the beta-sheets which may result in a greater surface exposure of an amino acid in one conformation than in another.