Document Detail

Prion amyloid structure explains templating: how proteins can be genes.
MedLine Citation:
PMID:  20726897     Owner:  NLM     Status:  MEDLINE    
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.
Reed B Wickner; Frank Shewmaker; Herman Edskes; Dmitry Kryndushkin; Julie Nemecek; Ryan McGlinchey; David Bateman; Chia-Lin Winchester
Related Documents :
10790727 - Prion diseases: a typical kuhnian abnormality in a molecular paradigm.
8972487 - Generation of monoclonal antibodies against human prion proteins in prp0/0 mice.
20920157 - Quantitative phosphoproteomic analysis of prion-infected neuronal cells.
8978027 - Genesis and variability of [psi] prion factors in saccharomyces cerevisiae.
2936307 - Crosslinking of actin filaments and inhibition of actomyosin subfragment-1 atpase activ...
16169847 - A three-dimensional working model of the multienzyme complex of aminoacyl-trna syntheta...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Review    
Journal Detail:
Title:  FEMS yeast research     Volume:  10     ISSN:  1567-1364     ISO Abbreviation:  FEMS Yeast Res.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-08     Completed Date:  2011-02-16     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  101085384     Medline TA:  FEMS Yeast Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  980-91     Citation Subset:  IM    
Copyright Information:
Journal compilation © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. No claim to original US government works.
Laboratory of Biochemistry and Genetics, National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Amyloid / chemistry*,  metabolism*
Glutathione Peroxidase / chemistry,  metabolism
Nuclear Magnetic Resonance, Biomolecular
Peptide Termination Factors / chemistry,  metabolism
Prions / chemistry*,  metabolism*
Saccharomyces cerevisiae / chemistry,  metabolism
Saccharomyces cerevisiae Proteins / chemistry*,  metabolism*
Grant Support
Reg. No./Substance:
0/Amyloid; 0/Peptide Termination Factors; 0/Prions; 0/RNQ1 protein, S cerevisiae; 0/SUP35 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; EC Peroxidase; EC protein, S cerevisiae

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Roles of multiple acyl-CoA oxidases in the routing of carbon flow towards ?-oxidation and polyhydrox...
Next Document:  A fungicidal piperazine-1-carboxamidine induces mitochondrial fission-dependent apoptosis in yeast.