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

Glutamine/asparagine (Q/N)-rich domains have a high propensity to form self -propagating amyloid fibrils. This phenomenon underlies both prion-based in heritance in yeast and aggregation of a number of proteins involved in huma n neurodegenerative diseases, To examine the prevalence of this phenomenon, complete proteomic sequences of 31 organisms and several incomplete proteo mic sequences were examined for Q/N-rich regions. We found that Q/N-rich re gions are essentially absent from the thermophilic bacterial and archaeal p roteomes. Moreover, the average Q/N content of the proteins in these organi sms is markedly lower than in mesophilic bacteria and eukaryotes, Mesophili c bacterial proteomes contain a small number (0-4) of proteins with Q/N-ric h regions. Remarkably, Q/N-rich domains are found in a much larger number o f eukaryotic proteins (107-472 per proteome) with diverse biochemical funct ions. Analyses of these regions argue they have been evolutionarily selecte d perhaps as modular "polar zipper" protein-protein interaction domains. Th ese data also provide a large pool of potential novel prion-forming protein s, two of which have recently been shown to behave as prions in yeast, thus suggesting that aggregation or prion-like regulation of protein function m ay be a normal regulatory process for many eukaryotic proteins with a wide variety of functions.