A comparative analysis between PrPc and PrPsc to determine the structure‐function relationship of protein misfolding in Scrapie prion disease

Abstract

The Minnetonka MSOE Center for BioMolecular Modeling SMART Team used 3D modeling and printing technology to examine structure‐function relationships of PrPsc. Scrapies is caused by prions, misfolded proteins in animals and humans, resulting in the development of fatal neurodegenerative encephalitis. Scrapies was one of the first prion diseases to be isolated and studied, and was found to be caused by the misfolding of the PrP protein into the PrPsc prion. We will do this by creating, annotating, and comparing two models, one of the original PrP protein, and one of the PrPsc prion. Scrapies disease is caused when the alpha‐helix rich prion protein (PrP) is converted into into a beta‐structure‐rich insoluble conformer (PrPsc) and is thought to be highly infectious. These structural changes in PrPsc contribute to its build up in the brain of sheep and goats PrP, leading to a deadly swelling of the brain. The buildup is caused by the inability of proteinase K (PK) to fully degrade PrPsc. PK has the ability to fully degrade PrP, but, interacting with PrPsc, can only create N terminally truncated PrPsc, resulting in a PK resistant core. There is currently no cure for Scrapies; however, further research is being done to discover how to reverse the functional effects of prion diseases. Our goal is to present which structural changes occur in the original protein PrP that cause the defective protein PrPsc, as well as determine how this misfolding occurs and what effect it has on the protein's function.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.