Author
|
Submitted to: Meeting Abstract
Publication Type: Abstract Only Publication Acceptance Date: 3/30/2015 Publication Date: 5/1/2015 Publication URL: http://www.tandfonline.com/doi/pdf/10.1080/19336896.2015.1033248 Citation: Silva, C.J., Erickson-Beltran, M.L. 2015. The chemistry of prions: small molecules, protein conformers and mass spectrometry. Meeting Abstract. Prion (Supplement 1) 9: S70. Interpretive Summary: Technical Abstract: Background/Introduction. Prions propagate by converting a normal cellular isoform (PrPC) into the prion isoform (PrPSc) in a template-driven process. The lysines in PrPC are highly conserved and strongly influence prion propagation, based on studies using natural polymorphisms of PrPC and transgenic animals expressing natural and unnatural PrPC polymorphisms. Materials and Methods. Prions from different hamster-adapted prion strains were reacted with small molecule reagents. The extent of this reaction was quantitated by mass spectrometry or Western blot-based analysis. Some samples were analyzed to quantitate the loss of infectivity associated with the corresponding lysine acetylation. Results and Conclusions. The reactivity of each of the prion strains with a given reagent was different. The strains showed differences in the reactivity of the N-terminal lysines, the C-terminal lysine and some of the lysines in the two large '-helicies. Western blotting showed differences in the lysine that was part of the epitope of the mAb 3F4. In addition, a relationship between the extent of the reaction of lysines and the loss of infectivity was observed. The approach of using differences in chemical reactivity can be be used understand the role of other amino acids in prion replication. In addition this approach can be used understand the role that lysines play in the propagation of other prion-like protein misfolding diseases such as AD, ALS, and PD. |
