The effects of amino acid composition on yeast prion formation and prion domain interactions.
Yeast prions provide a powerful model system for examining prion formation and propagation in vivo. Yeast prion formation is driven primarily by amino acid composition, not by primary amino acid sequence. However, although yeast prion domains are consistently glutamine/asparagine-rich, they otherwise vary significantly in their compositions. Therefore, elucidating the exact compositional requirements for yeast prion formation has proven challenging. We have developed an in vivo method that allows for estimation of the prion propensity of each amino acid within the context of a yeast prion domain.(1) Using these values, we are able to predict the prion-propensity of various glutamine/asparagine-rich yeast domains. These results provide insight into the basis for yeast prion formation, and may aid in the discovery of additional novel prion domains. Additionally, we examined whether amino acid composition could drive interactions between heterologous glutamine/asparagine-rich proteins.(2) Although inefficient interactions between yeast prion domains have previously been observed, we found that one prion protein, Ure2, is able to interact with compositionally similar domains with unprecedented efficiency. This observation, combined with the growing number of yeast prions, suggests that a broad network of interactions between heterologous glutamine/asparagine-rich proteins may affect yeast prion formation.
Ross
Eric D
ED
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA. eric.ross@colostate.edu
Toombs
James A
JA
D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D001216:Asparagine / Q000737:chemistry / Q000378:metabolism; D019295:Computational Biology; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D005973:Glutamine / Q000737:chemistry / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000737:chemistry / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism
D000596:Amino Acids; D005656:Fungal Proteins; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; D005973:Glutamine; D001216:Asparagine; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae