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Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6519-24. doi: 10.1073/pnas.1119366109. Epub 2012 Apr 2.

De novo design of synthetic prion domains.

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1
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.

Abstract

Prions are important disease agents and epigenetic regulatory elements. Prion formation involves the structural conversion of proteins from a soluble form into an insoluble amyloid form. In many cases, this structural conversion is driven by a glutamine/asparagine (Q/N)-rich prion-forming domain. However, our understanding of the sequence requirements for prion formation and propagation by Q/N-rich domains has been insufficient for accurate prion propensity prediction or prion domain design. By focusing exclusively on amino acid composition, we have developed a prion aggregation prediction algorithm (PAPA), specifically designed to predict prion propensity of Q/N-rich proteins. Here, we show not only that this algorithm is far more effective than traditional amyloid prediction algorithms at predicting prion propensity of Q/N-rich proteins, but remarkably, also that PAPA is capable of rationally designing protein domains that function as prions in vivo.

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PMID:
22474356
PMCID:
PMC3340034
DOI:
10.1073/pnas.1119366109
[Indexed for MEDLINE]
Free PMC Article
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