title: A census of glutamine/asparagine-rich regions: implications for their conserved function and the prediction of novel prions.
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.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-0450, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Michelitsch
authors.forename: J S
authors.initials: JS
authors.lastname: Weissman
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000096:biosynthesis; D001216:Asparagine / Q000737:chemistry / Q000378:metabolism*; D003062:Codon; D005973:Glutamine / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000682:Amyloid; D003062:Codon; D011328:Prions; D005973:Glutamine; D001216:Asparagine