Editor: Monique Bolotin-Fukuhara
Prion amyloid structure explains templating: how proteins can be genes
Article first published online: 5 NOV 2010
Journal compilation © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. No claim to original US government works
FEMS Yeast Research
Special Issue: Yeasts as a Model for Human Diseases
Volume 10, Issue 8, pages 980–991, December 2010
How to Cite
Wickner, R. B., Shewmaker, F., Edskes, H., Kryndushkin, D., Nemecek, J., McGlinchey, R., Bateman, D. and Winchester, C.-L. (2010), Prion amyloid structure explains templating: how proteins can be genes. FEMS Yeast Research, 10: 980–991. doi: 10.1111/j.1567-1364.2010.00666.x
- Issue published online: 5 NOV 2010
- Article first published online: 5 NOV 2010
- Received 17 February 2010; revised 7 June 2010; accepted 12 July 2010.Final version published online 18 August 2010.
- in-register parallel structure
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.