Polythreonine aggregation and yeast prion [PSI+]

Abstract

Protein aggregation is the self-assembly of misfolded proteins which underlies most late-onset neurodegenerative diseases. Previous studies have shown that one of the main causes of protein aggregation is the expansion of nucleotide repeats. In this study, I attempted to characterize polythreonine (polyT) that the laboratory of Prof. Choe identified as a protein aggregation motif. By using western blot and fluorescence microscopy, I showed that polyT exhibits amyloid-like characteristics, including the detergent resistance and the seeding effect that facilitates aggregation of other proteins with shorter polythreonine stretches. I asked if the polythreonine sequence can replace another amyloidogenic protein domain. The N-terminal domain of yeast Sup35 was replaced with 10 or 14 polythreonine stretches to examine if polythreonine can form and maintain the [PSI+] prion phenotype. However, I could not observe the appearance of [PSI+] prion using cells genetically modified to introduce polyT. Therefore, physicochemical characters of polyT remains to be studied further.