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

Microbial Cell Factories

Sedky Hassan¹  Joaquín Castilla²  Fei Wang³  Witold K. Surewicz⁴  Mentor Mulaj⁴  Lewis S. Zou⁵  Zerui Wang⁵  Wen-Quan Zou⁵  Johnny Dang⁵  Pingping Shen⁵  Hisashi Fujioka⁶  Ameer Elfarash⁷  Jan Steyaert⁸  Romany Abskharon⁸  Alexandre Wohlkonig⁸ 

[1] Botany Department, Faculty of Science, Assiut University, New Valley Branch;CIC bioGUNE, Parque Tecnológico de Bizkaia;Center for Neurodegenerative Science, Van Andel Research Institute;Department of Physiology and Biophysics, Case Western Reserve University School of Medicine;Departments of Pathology, Case Western Reserve University School of Medicine;Electron Microscopy Core Facility, Case Western Reserve University School of Medicine;Genetic Department, Faculty of Agriculture, Assiut University;VIB Center for Structural Biology, VIB;

关键词: Prions;    Prion protein;    Prion diseases;    Quiescin sulfhydryl oxidase (QSOX);    Bank vole;    Thioflavin T (ThT);   

DOI  :  10.1186/s12934-017-0782-x

来源: DOAJ

【 摘 要 】

Abstract Background The infectious prion protein (PrPSc or prion) is derived from its cellular form (PrPC) through a conformational transition in animal and human prion diseases. Studies have shown that the interspecies conversion of PrPC to PrPSc is largely swayed by species barriers, which is mainly deciphered by the sequence and conformation of the proteins among species. However, the bank vole PrPC (BVPrP) is highly susceptible to PrPSc 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.

【 授权许可】

Unknown