Prion protein exists in two different isoforms, a normal cellular isoform (PrP C) and an abnormal infectious isoform (PrP Sc), the latter is a causative agent of prion disease such as mad cow disease and Creutzfeldt-Jakob disease. Amino acid sequences of PrP C and PrP Sc are identical, but their conformations are rather different; PrP C rich in non β-sheet vs. PrP Sc rich in β-sheet isoform. Since the two isoforms have quite different conformation, this host factor might be a molecular chaperone, which enables to override an energy barrier between PrP C and PrP Sc. To examine the protein unfolding activities against collectly folded structure exist or not, we constructed an assay system and purified a novel molecular chaperone, Unfoldin, from S. cerevisiae. Unfoldin consists of oligomeric ring-like structure with the central cavity and has an ATP-dependent protein unfolding activity with broad specificity in vitro, of which targets included PrP in β-sheet form, α-synuclein, and Aβ protein. We have also found that mouse neuroblastoma N2a cells contained the activity. Treatment of this factor with an ATP-hydrolyzing enzyme, apyrase, caused the decrease in its protein unfolding activity. It was suggested that the purified protein probably formed homo-oligomer consisting of 4-5 subunits and its activity was ATP-dependent.
|出版ステータス||Published - 2003 11月 1|
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