NR AJVB
AU Radulescu,R.T.; Korth,C.
TI Prion function and dysfunction: a structure-based scenario.
QU Medical Hypotheses 1996 Mar; 46(3): 225-8
PT journal article
AB 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.
IN Die Autoren glauben, im Prionprotein eine potentielle Bindungsstelle für Nicotinamidadenindinucleotid (NADH)gefunden zu haben. Außerdem sollen die Oktapeptidwiederholungen eine Homologie zu den nukleinsäurebindenden und einzelstrangannähernden Oktapeptidwiederholungen der Säugerribonukleoproteine (RNP) A1. Daher halten sie es für möglich, dass das Prionprotein eine NADH-abhängige Oxidoreduktaseaktivität besitzt und Nukleinsäuren splicen und zu Dopplesträngen zusammenführen kann. Sie glauben außerdem, dass ribozymartige Nukleinsäuren an der Umwandlungsreaktion der Prionproteine beteiligt sein könnten.
ZR 33
MH Amino Acid Sequence/genetics; Animal; DNA Probes/diagnostic use; DNA Replication/genetics; Hamsters; Human; Molecular Sequence Data; Nucleic Acid Heteroduplexes/genetics; Prion Diseases/*physiopathology; Prions/genetics/*pathogenicity; Repetitive Sequences, Nucleic Acid/genetics; Virus Replication/genetics
SP englisch
PO England