[Unfolding chaperone as a prion protein relating molecule].
Prion protein exists in two different isoforms, a normal cellular isoform (PrPc) and an abnormal infectious isoform (PrPSc), the latter is a causative agent of prion disease such as mad cow disease and Creutzfeldt-Jakob disease. Amino acid sequences of PrPc and PrPSc are identical, but their conformations are rather different; PrPc rich in non beta-sheet vs. PrPSc rich in beta-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 PrPc and PrPSc. To examine the protein unfolding activities against collectively folded structure exist or not, we constructed an assay system and purified a novel molecular chaperone. Unfolding, from S. cerevisiae. Unfolding consists of oligomeric ring-like structure with the central cavity and has an ATP-dependent protein Unfoldingg activity with broad specificity in vitro, of which targets included PrP in beta-sheet form, alpha-synuclein, and A beta 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 Unfoldingg activity. It was suggested that the purified protein probably formed homo-oligomer consisting of 4-5 subunits and its activity was ATP-dependent.
Hachiya
Naomi S
NS
Sakasegawa
Yuji
Y
Kaneko
Kiyotoshi
K
D000255:Adenosine Triphosphate; D000818:Animals; D001081:Apyrase; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones / Q000737:chemistry* / Q000502:physiology; D018621:PrPC Proteins / Q000737:chemistry / Q000378:metabolism*; D018620:PrPSc Proteins / Q000737:chemistry / Q000378:metabolism*; D017096:Prion Diseases / Q000209:etiology; D011487:Protein Conformation; D017510:Protein Folding; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000502:physiology; D017386:Sequence Homology, Amino Acid
D018832:Molecular Chaperones; D018621:PrPC Proteins; D018620:PrPSc Proteins; D029701:Saccharomyces cerevisiae Proteins; C488472:unfolding protein, S cerevisiae; D000255:Adenosine Triphosphate; D001081:Apyrase