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

Microbial Cell Factories

Research

Sedky Hassan¹  Joaquín Castilla²  Fei Wang³  Witold K. Surewicz⁴  Mentor Mulaj⁴  Lewis S. Zou⁵  Johnny Dang⁵  Wen-Quan Zou⁶  Pingping Shen⁷  Zerui Wang⁷  Hisashi Fujioka⁸  Ameer Elfarash⁹  Alexandre Wohlkonig^1,10  Jan Steyaert^1,10  Romany Abskharon^1,11 

[1] Botany Department, Faculty of Science, Assiut University, New Valley Branch, 72511, El-Kharja, Egypt;CIC bioGUNE, Parque Tecnológico de Bizkaia, 48160, Derio, Bizkaia, Spain;IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Bizkaia, Spain;Center for Neurodegenerative Science, Van Andel Research Institute, 49503, Grand Rapids, MI, USA;Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH, USA;Departments of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA;Departments of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA;Departments of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA;National Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA;National Center for Regenerative Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA;The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China;State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China;Departments of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA;The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China;Electron Microscopy Core Facility, Case Western Reserve University School of Medicine, Cleveland, OH, USA;Genetic Department, Faculty of Agriculture, Assiut University, 71516, Assuit, Egypt;VIB Center for Structural Biology, VIB, 1050, Brussels, Belgium;Structural Biology Brussels, Vrije Universiteit Brussel (VUB), 1050, Brussels, Belgium;VIB Center for Structural Biology, VIB, 1050, Brussels, Belgium;Structural Biology Brussels, Vrije Universiteit Brussel (VUB), 1050, Brussels, Belgium;National Institute of Oceanography and Fisheries (NIFO), 11516, Cairo, Egypt;Center for Neurodegenerative Science, Van Andel Research Institute, 49503, Grand Rapids, MI, USA;

关键词: Prions;    Prion protein;    Prion diseases;    Quiescin sulfhydryl oxidase (QSOX);    Bank vole;    Thioflavin T (ThT);    Surface plasmon resonance (SPR);    Electron microscopy;    Circular dichroism;    Aggregation;   

DOI  :  10.1186/s12934-017-0782-x

 received in 2017-05-02, accepted in 2017-09-21,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsTo 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.ConclusionsOur 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】

CC BY   
© The Author(s) 2017