title: Prion amyloid structure explains templating: how proteins can be genes.
abstract: The yeast and fungal prions determine heritable and infectious traits, and are thus genes composed of protein. Most prions are inactive forms of a normal protein as it forms a self-propagating filamentous β-sheet-rich polymer structure called amyloid. Remarkably, a single prion protein sequence can form two or more faithfully inherited prion variants, in effect alleles of these genes. What protein structure explains this protein-based inheritance? Using solid-state nuclear magnetic resonance, we showed that the infectious amyloids of the prion domains of Ure2p, Sup35p and Rnq1p have an in-register parallel architecture. This structure explains how the amyloid filament ends can template the structure of a new protein as it joins the filament. The yeast prions [PSI(+)] and [URE3] are not found in wild strains, indicating that they are a disadvantage to the cell. Moreover, the prion domains of Ure2p and Sup35p have functions unrelated to prion formation, indicating that these domains are not present for the purpose of forming prions. Indeed, prion-forming ability is not conserved, even within Saccharomyces cerevisiae, suggesting that the rare formation of prions is a disease. The prion domain sequences generally vary more rapidly in evolution than does the remainder of the molecule, producing a barrier to prion transmission, perhaps selected in evolution by this protection.
authors: Laboratory of Biochemistry and Genetics, National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. wickner@helix.nih.gov
authors: Reed B
authors: RB
authors: Wickner
authors: Frank
authors: F
authors: Shewmaker
authors: Herman
authors: H
authors: Edskes
authors: Dmitry
authors: D
authors: Kryndushkin
authors: Julie
authors: J
authors: Nemecek
authors: Ryan
authors: R
authors: McGlinchey
authors: David
authors: D
authors: Bateman
authors: Chia-Lin
authors: CL
authors: Winchester
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D010454:Peptide Termination Factors / Q000737:chemistry / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000682:Amyloid; D010454:Peptide Termination Factors; D011328:Prions; C404807:RNQ1 protein, S cerevisiae; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae