Prion function and dysfunction: a structure-based scenario.
Prion diseases are transmissible, neurodegenerative disorders associated with as yet incompletely defined isoforms of a cellular protein termed prion protein (PrP). We have now identified in PrP structural information compatible with nucleotide- and nucleic acid-binding. As such, PrP contains a putative nicotinamide adenine dinucleotide (NADH)-binding site. Moreover, the PrP octarepeats reveal homology to the nucleic acid-binding and strand-annealing octarepeats of mammalian heterogeneous ribonucleoprotein (RNP) A1. Therefore, PrP may have NADH-dependent oxidoreductase activity as well as A1-like functions such as nucleic acid annealing and splicing. Moreover, we propose that infectious prions are propagated through a dynamic molecular symbiosis between a ribozyme-like nucleic acid and a conformational isomer of the RNP-like prion protein. Thus, our model has important implications for the understanding and treatment of prion diseases.
Radulescu
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Korth
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D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D006224:Cricetinae; D015342:DNA Probes; D004261:DNA Replication / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics; D017096:Prion Diseases / Q000503:physiopathology*; D011328:Prions / Q000235:genetics / Q000472:pathogenicity*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
D015342:DNA Probes; D009692:Nucleic Acid Heteroduplexes; D011328:Prions