Comparative Analysis of Prions Among Mammals with TSEs

Vanessa Alexandra

Prions are self-replicating infectious agents composed entirely of proteins. The normal physiological form of the prion protein, PrPC, is a cell-surface glycoprotein found in many tissues throughout the body but primarily in the nervous system.1 Misfolding of the prion protein into its infectious isoform, PrPSc, can cause fatal neurodegenerative diseases called transmissible spongiform encephalopathies (TSEs).2 Research has suggested that the conversion of alpha helices to beta sheets plays an important role in the infectious nature of PrPSc. More knowledge about prions could help with treatment of these diseases, but little is known about the misfolding mechanism of the prion protein and the structure of the infectious prion protein.

This project seeks to discover similarities and differences in amino acid frequencies and structures of 5 different mammals with known TSEs. The 5 mammals that will be studied in this project are Homo sapiensBos taurus (cattle), Ovis aries (sheep), Cervus elaphus nelsoni (Rocky Mountain elk), and Felis catus (cat). Prions are known to cause Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep, chronic wasting disease (CWD) in deer and eld, and feline spongiform encephalopathy in cats.3 A comparative analysis will be conducted, and it will include calculating amino acid frequencies, creating a sequence alignment, and doing a statistical analysis using paired t-tests. Based on the comparative analysis that will be conducted, an attempt will be made to explain any differences discovered and to identify important elements that play a role in the misfolding of the prion protein.