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Viruses 2014, 6(10), 3907-3924; doi:10.3390/v6103907

Protein Folding Activity of the Ribosome (PFAR) –– A Target for Antiprion Compounds

Department of Cell and Molecular Biology, Uppsala University, Box-596, BMC, Uppsala SE-75124, Sweden
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Received: 15 August 2014 / Revised: 13 October 2014 / Accepted: 15 October 2014 / Published: 23 October 2014
(This article belongs to the Special Issue Recent Developments in the Prion Field)
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Abstract

Prion diseases are fatal neurodegenerative diseases affecting mammals. Prions are misfolded amyloid aggregates of the prion protein (PrP), which form when the alpha helical, soluble form of PrP converts to an aggregation-prone, beta sheet form. Thus, prions originate as protein folding problems. The discovery of yeast prion(s) and the development of a red-/white-colony based assay facilitated safe and high-throughput screening of antiprion compounds. With this assay three antiprion compounds; 6-aminophenanthridine (6AP), guanabenz acetate (GA), and imiquimod (IQ) have been identified. Biochemical and genetic studies reveal that these compounds target ribosomal RNA (rRNA) and inhibit specifically the protein folding activity of the ribosome (PFAR). The domain V of the 23S/25S/28S rRNA of the large ribosomal subunit constitutes the active site for PFAR. 6AP and GA inhibit PFAR by competition with the protein substrates for the common binding sites on the domain V rRNA. PFAR inhibition by these antiprion compounds opens up new possibilities for understanding prion formation, propagation and the role of the ribosome therein. In this review, we summarize and analyze the correlation between PFAR and prion processes using the antiprion compounds as tools. View Full-Text
Keywords: Prion; antiprion compounds; amyloid; protein folding; PFAR; ribosome; ribosomal RNA; domain V; 23S rRNA Prion; antiprion compounds; amyloid; protein folding; PFAR; ribosome; ribosomal RNA; domain V; 23S rRNA
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Banerjee, D.; Sanyal, S. Protein Folding Activity of the Ribosome (PFAR) –– A Target for Antiprion Compounds. Viruses 2014, 6, 3907-3924.

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