title: Manganese-induced changes of the biochemical characteristics of the recombinant wild-type and mutant PrPs.
abstract: Manganese may play some roles in the pathogenesis of prion diseases. In this study, recombinant human wild-type (WT) PrP and PrP mutants with deleted or inserted octarepeats were exposed to manganese, and their biochemical and biophysical characteristics were evaluated by proteinase K (PK) digestion, sedimentation experiments, transmission electron microscopy and circular dichroism. It demonstrated that incubation of manganese remarkably increased PK-resistances, protein aggregations and beta-sheet contents of the PrPs. Moreover, the PrP mutants of inserted or deleted octarepeats were much vulnerable to the influence of manganese, which showed obviously more aggregation and higher beta-sheet content than that of WT-PrP. It highlights that the effect of manganese on the PrP seems to lie on the incorrectness of the octarepeats numbers. The association of the octarepeats number of PrP with manganese may further provide insight into the unresolved biological function of PrP in the neurons.
authors.affiliation: 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.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Li
authors.forename: Chen-Fang
authors.initials: CF
authors.lastname: Dong
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Wang
authors.forename: Rui-Min
authors.initials: RM
authors.lastname: Zhou
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.forename: Chan
authors.initials: C
authors.lastname: Tian
authors.forename: Chen
authors.initials: C
authors.lastname: Gao
authors.forename: Guo-Yong
authors.initials: GY
authors.lastname: Mei
authors.forename: Cao
authors.initials: C
authors.lastname: Chen
authors.forename: Kun
authors.initials: K
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
mesh_terms: D002942:Circular Dichroism; D006801:Humans; D008345:Manganese / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D011328:Prions / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D020449:Repetitive Sequences, Amino Acid
chemical_list: D011328:Prions; D011994:Recombinant Proteins; D008345:Manganese