A census of glutamine/asparagine-rich regions: Implications for their conserved function and the prediction of novel prions

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Abstract
Glutamine/asparagine (Q/N)-rich domains have a high propensity to form self-propagating amyloid fibrils. This phenomenon underlies both prion-based inheritance in yeast and aggregation of a number of proteins involved in human neurodegenerative diseases. To examine the prevalence of this phenomenon, complete proteomic sequences of 31 organisms and several incomplete proteomic sequences were examined for Q/N-rich regions. We found that Q/N-rich regions are essentially absent from the thermophilic bacterial and archaeal proteomes. Moreover, the average Q/N content of the proteins in these organisms is markedly lower than in mesophilic bacteria and eukaryotes. Mesophilic bacterial proteomes contain a small number (0–4) of proteins with Q/N-rich regions. Remarkably, Q/N-rich domains are found in a much larger number of eukaryotic proteins (107–472 per proteome) with diverse biochemical functions. Analyses of these regions argue they have been evolutionarily selected perhaps as modular “polar zipper” protein–protein interaction domains. These data also provide a large pool of potential novel prion-forming proteins, two of which have recently been shown to behave as prions in yeast, thus suggesting that aggregation or prion-like regulation of protein function may be a normal regulatory process for many eukaryotic proteins with a wide variety of functions.