Soluble polymorphic bank vole prion proteins induced by co-expression of quiescin sulfhydryl oxidase in E. coli and their aggregation behaviors.

TitleSoluble polymorphic bank vole prion proteins induced by co-expression of quiescin sulfhydryl oxidase in E. coli and their aggregation behaviors.
Publication TypeJournal Article
Year of Publication2017
AuthorsAbskharon, R., J. Dang, A. Elfarash, Z. Wang, P. Shen, L. S. Zou, S. Hassan, F. Wang, H. Fujioka, J. Steyaert, M. Mulaj, W. K. Surewicz, J. Castilla, A. Wohlkonig, and W-Q. Zou
JournalMicrob Cell Fact
Volume16
Issue1
Pagination170
Date Published2017 Oct 04
ISSN1475-2859
KeywordsAnimals, Arvicolinae, Circular Dichroism, Escherichia coli, Humans, Mice, Mice, Transgenic, Microscopy, Electron, Oxidoreductases, Polymorphism, Genetic, Prion Diseases, Prion Proteins, Prions, Protein Aggregates, PrPC Proteins, Surface Plasmon Resonance, Thiazoles
Abstract

BACKGROUND: The infectious prion protein (PrP or prion) is derived from its cellular form (PrP) through a conformational transition in animal and human prion diseases. Studies have shown that the interspecies conversion of PrP to PrP is largely swayed by species barriers, which is mainly deciphered by the sequence and conformation of the proteins among species. However, the bank vole PrP (BVPrP) is highly susceptible to PrP from different species. Transgenic mice expressing BVPrP with the polymorphic isoleucine (109I) but methionine (109M) at residue 109 spontaneously develop prion disease.RESULTS: To explore the mechanism underlying the unique susceptibility and convertibility, we generated soluble BVPrP by co-expression of BVPrP with Quiescin sulfhydryl oxidase (QSOX) in Escherichia coli. Interestingly, rBVPrP-109M and rBVPrP-109I exhibited distinct seeded aggregation pathways and aggregate morphologies upon seeding of mouse recombinant PrP fibrils, as monitored by thioflavin T fluorescence and electron microscopy. Moreover, they displayed different aggregation behaviors induced by seeding of hamster and mouse prion strains under real-time quaking-induced conversion.CONCLUSIONS: Our results suggest that QSOX facilitates the formation of soluble prion protein and provide further evidence that the polymorphism at residue 109 of QSOX-induced BVPrP may be a determinant in mediating its distinct convertibility and susceptibility.

DOI10.1186/s12934-017-0782-x
Alternate JournalMicrob. Cell Fact.
PubMed ID28978309
PubMed Central IDPMC5628483
Grant ListP01 AI106705 / AI / NIAID NIH HHS / United States
R01 NS083687 / NS / NINDS NIH HHS / United States
R21 NS087588 / NS / NINDS NIH HHS / United States
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