Alcohol oxidase (AOX1) from Pichia pastoris is a novel inhibitor of prion propagation and a potential ATPase |
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Authors: | Hong Zhang Harriët M Loovers Li-Qiong Xu Mingzhu Wang Pamela J E Rowling Laura S Itzhaki Weimin Gong Jun-Mei Zhou Gary W Jones Sarah Perrett |
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Institution: | National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.; Graduate School of the Chinese Academy of Sciences, Beijing 100039, China.; Department of Biology, National University of Ireland Maynooth, Maynooth, Co. Kildare, Ireland.; MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 0XZ, UK. |
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Abstract: | Previous results suggest that methylotrophic yeasts may contain factors that modulate prion stability. Alcohol oxidase (AOX), a key enzyme in methanol metabolism, is an abundant protein that is specific to methylotrophic yeasts. We examined the effect of Pichia pastoris AOX1 on prion phenotypes in Saccharomyces cerevisiae . The S. cerevisiae prion states PSI +] and URE3 ] arise from aggregation of the proteins Sup35p and Ure2p respectively, and correlate with the ability of Sup35p and Ure2p to form amyloid-like fibrils in vitro . We found that expression of P. pastoris AOX1 in S. cerevisiae had no effect on propagation of the PSI +] prion, but inhibited propagation of URE3 ]. Addition of AOX1 early in the time-course of fibril formation inhibits Ure2p fibril formation in vitro . AOX1 has not previously been identified as an ATPase. However, we discovered that in addition to its flavin adenine dinucleotide-dependent AOX activity, AOX1 possesses ATPase activity. This study identifies AOX1 as a novel prion inhibitory factor and a potential ATPase. |
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