DETECTION OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY AGENTS IN LIVESTOCK, WILDLIFE, AGRICULTURAL PRODUCTS, AND THE ENVIRONMENT
Location: Foodborne Contaminants Research
Title: Structural organization of mammalian prions as probed by limited proteolysis
| Vasquez-Fernandez, Ester - |
| Alonso, Jana - |
| Pastrana, Miguel - |
| Ramos, Adriana - |
| Stitz, Lothar - |
| Vidal, Enric - |
| Dynin, Irina |
| Petsch, Benjamin - |
| Requena, Jesus - |
Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 15, 2012
Publication Date: November 20, 2012
Citation: Vasquez-Fernandez, E., Alonso, J., Pastrana, M.A., Ramos, A., Stitz, L., Vidal, E., Dynin, I.A., Petsch, B., Silva, C.J., Requena, J.R. 2012. Structural organization of mammalian prions as probed by limited proteolysis. PLoS One. 7(11):e50111. doi:10.1371/journal.pone.0050111.
Interpretive Summary: PrP is a protein. When its shape is changed it is involved in a type of brain diseases known as Transmissible Spongiform Encephalopathy (TSE). TSEs include Bovine Spongiform Encephalopathy in cows (BSE, or "mad cow" disease), Chronic Wasting Disease in deer (CWD), and scrapie in sheep. Theses changes in the shape of PrP are not understood and we need to understand them better to better understand the disease. To do this, we studied a special form of PrP from a unique breed of mice (GPI-) that changes its shape, but does not cause a TSE disease. The PrP from these mice is missing a part of the protein that attaches it to the nerve cell surface. We found that the changed form of PrP from GPI- mice resembles a short four-rung ladder and that this four-rung ladder shape is common to the TSE causing PrP found in other animals.
The GPI- transgenic mouse model was used to study the structure of GPI- prions. We obtained valuable information about the structure of prions by performing limited proteolysis of the GPI- prions and analyzing the results by mass spectrometry and Western blot. This information coupled with previous results provides experimental evidence to support a general prion structure consisting of a series of protease-resistant ''sheets connected by protease-sensitive flexible loops and turns.