Modeling the Conversion of Normal Protein PrPC into the Mutated PrPSC in a Prion Disease

Modeling the Conversion of Normal Protein PrPC into the Mutated PrPSC in a Prion Disease

Gerstmann-Straussler-Scheinker (GSS) is a rare, genetically inherited prion disease caused by a mutation in the prion gene (PRNP). Carriers begin to experience GSS symptoms (similar to Parkinson's and Alzheimer's) during their 30s and 40s. While molecular details concerning the progression of GSS remain largely unknown, the altered conformation of the prion could be directly involved in the aggregation of plaques contributing to progression of the disease. In collaboration with the Milwaukee School of Engineering (MSOE) Center for Biomolecular Modeling - Students Modeling A Research Topic (CBM-SMART) program, we used 3-D modeling and printing technology to examine relationships between this normal and mutated prion. Details of the normal GSS prion structure (PrPC) from the Protein Data Bank (PDB) File, 3HAK, were imported into Jmol, a protein visualization software. The molecular changes in the prion protein that were highlighted include a mutation in which phenylalanine becomes serine at position 198, a loop from residues 193-197 which becomes absent, and the alpha helix structure at residues 164 - 170 which becomes malformed due to the formation of a salt bridge between arginine 164 and aspartic acid 167. The N- and C- termini of the prion were also highlighted. This model can be used by genetic counselors, physicians, and researchers to educate the public on the molecular changes associated with prion diseases like GSS.