title: Quiescin-sulfhydryl oxidase inhibits prion formationin vitro.
abstract: Prions are infectious proteins that cause a group of fatal transmissible diseases in animals and humans. The scrapie isoform (PrPSc) of the cellular prion protein (PrPC) is the only known component of the prion. Several lines of evidence have suggested that the formation and molecular features of PrPScare associated with an abnormal unfolding/refolding process. Quiescin-sulfhydryl oxidase (QSOX) plays a role in protein folding by introducing disulfides into unfolded reduced proteins. Here we report that QSOX inhibits human prion propagation in protein misfolding cyclic amplification reactions and murine prion propagation in scrapie-infected neuroblastoma cells. Moreover, QSOX preferentially binds PrPScfrom prion-infected human or animal brains, but not PrPCfrom uninfected brains. Surface plasmon resonance of the recombinant mouse PrP (moPrP) demonstrates that the affinity of QSOX for monomer is significantly lower than that for octamer (312 nM vs 1.7 nM). QSOX exhibits much lower affinity for N-terminally truncated moPrP (PrP89-230) than for the full-length moPrP (PrP23-231) (312 nM vs 2 nM), suggesting that the N-terminal region of PrP is critical for the interaction of PrP with QSOX. Our study indicates that QSOX may play a role in prion formation, which may open new therapeutic avenues for treating prion diseases.
authors.affiliation: First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China.|Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Zhan
authors.affiliation: 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.|CNS, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: Romany
authors.initials: R
authors.lastname: Abskharon
authors.affiliation: First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China.|Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Jue
authors.initials: J
authors.lastname: Yuan
authors.affiliation: First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China.|Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Johnny
authors.initials: J
authors.lastname: Dang
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Manuel Camacho
authors.initials: MC
authors.lastname: Martinez
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.|Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, The People's Republic of China.
authors.forename: Zerui
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Hôpital Lariboisière, Service d'Anatomie et Cytologie Pathologiques, Paris, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Mikol
authors.affiliation: IRMB -Hôpital ST ELOI, CHU de Montpellier, Montpellier, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann
authors.affiliation: Diabetes Research Center, Ningbo University, The People's Republic of China.
authors.forename: Shizhong
authors.initials: S
authors.lastname: Bu
authors.affiliation: VIB Center for Structural Biology, VIB, 1050 Brussels, Belgium.|Structural Biology Brussels, Vrije Universiteit Brussel (VUB), 1050 Brussels, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Steyaert
authors.affiliation: Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, The People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.|Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.|Department of Neuroscience, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Petersen
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.|Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Kong
authors.affiliation: First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China.
authors.forename: Gong-Xiang
authors.initials: GX
authors.lastname: Wang
authors.affiliation: VIB Center for Structural Biology, VIB, 1050 Brussels, Belgium.|Structural Biology Brussels, Vrije Universiteit Brussel (VUB), 1050 Brussels, Belgium.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Wohlkonig
authors.affiliation: First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People's Republic of China.|Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.|Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.|National Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.|Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, The 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, The People's Republic of China.
authors.forename: Wen-Quan
authors.initials: WQ
authors.lastname: Zou
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D017510:Protein Folding; D012608:Scrapie / Q000378:metabolism*; D050862:Oxidoreductases Acting on Sulfur Group Donors
chemical_list: D010088:Oxidoreductases; D011328:Prions; D050862:Oxidoreductases Acting on Sulfur Group Donors
keywords: Quiescin sulfhydryl oxidase (QSOX); prions; protein misfolding cyclic amplification; recombinant prion protein; scrapie-infected mouse neuroblastoma cells (ScN2a)