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PMID: 25341659 Published · epublish English Journal Article Research Support, Non-U.S. Gov't Review

Protein folding activity of the ribosome (PFAR) -- a target for antiprion compounds.

Viruses ·Vol. 6 ·No. 10 ·2014-10-23 ·Pages 3907-24

Banerjee D, Sanyal S

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.

MeSH Terms
Aminoquinolines/pharmacology Binding Sites Guanabenz/pharmacology Humans Imiquimod Phenanthridines/pharmacology Prion Diseases/drug therapy Prions/chemistry,drug effects Protein Folding/drug effects RNA, Ribosomal/metabolism Ribosomes/drug effects,physiology
Chemicals
6-aminophenanthridine Aminoquinolines Phenanthridines Prions RNA, Ribosomal Guanabenz Imiquimod
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Banerjee Debapriya
Department of Cell and Molecular Biology, Uppsala University, Box-596, BMC, Uppsala SE-75124, Sweden. debapriya.banerjee@icm.uu.se.
Sanyal Suparna
Department of Cell and Molecular Biology, Uppsala University, Box-596, BMC, Uppsala SE-75124, Sweden. suparna.sanyal@icm.uu.se.
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Article Info
Journal
Viruses
Abbr.
Viruses
ISSN
1999-4915
DOI
10.3390/v6103907
Email
debapriya.banerjee@icm.uu.se
suparna.sanyal@icm.uu.se
Published
2014-10-23
Epub
2014-00-23
Pages
3907-24
Language
English
Region
Switzerland
NLM ID
101509722
PMCID
PMC4213570
Subset
IM
External Links
PubMed source DOI: 10.3390/v6103907 PMC Full Text View journal details
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