Prion function and dysfunction: a structure-based scenario.

R T Radulescu; C Korth

doi:10.1016/s0306-9877(96)90245-5

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Prion function and dysfunction: a structure-based scenario.

R T Radulescu·C Korth

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Abstract

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.

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Amino Acid Sequence Animals Cricetinae DNA Probes DNA Replication Humans Molecular Sequence Data Nucleic Acid Heteroduplexes Prion Diseases Prions Repetitive Sequences, Nucleic Acid Virus Replication Journal Article

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R T Radulescu, C Korth. 1996. Prion function and dysfunction: a structure-based scenario.. https://doi.org/10.1016/s0306-9877(96)90245-5

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