title: Heat shock protein 104 inhibited the fibrillization of prion peptide 106-126 and disassembled prion peptide 106-126 fibrils in vitro.
abstract: Amyloid-like fibrils have been associated with the pathogenesis of human prion diseases. Prion peptide of aa 106-126 (PrP106-126) exhibits many PrP(Sc)-like biochemical features, forming amyloid-like fibrils in vitro. Here, we found that the recombinant yeast-derived molecular chaperon Hsp104 inhibited significantly the fibril assembly of the synthetic PrP106-126 peptide by dynamic ThT assays in vitro. EM assays revealed almost no fibril-like structure after incubation of the synthetic PrP106-126 peptides with Hsp104 for 12h. Circular dichroism assays identified that treatment of Hsp104 shifted the secondary structure of PrP106-126 fibrils from β-sheet to a random coil. MTT tests confirmed that interaction of PrP106-126 with Hsp104 maintained the toxicity of PrP106-126 on human neuroblastoma cell line SK-N-SH. Additionally, Hsp104 was able to disassemble the mature PrP106-126 fibrils in vitro, leading to recovering the cytotoxicity of PrP106-126 on SK-N-SH cells. Our study provides the molecular evidences that the yeast-derived Hsp104 can interfere in the fibril assembly and disassembly of human PrP106-126 segment.
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, Ying-Xin Rd 100, Beijing 100052, People's Republic of China.
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Liu
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Han
authors.forename: Juan
authors.initials: J
authors.lastname: Song
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Jing
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.forename: Chan
authors.initials: C
authors.lastname: Tian
authors.forename: Zhao-Yun
authors.initials: ZY
authors.lastname: Wang
authors.forename: Chao-Ping
authors.initials: CP
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D005656:Fungal Proteins / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000633:toxicity; D011328:Prions / Q000737:chemistry* / Q000633:toxicity; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary / Q000187:drug effects; D058767:Protein Unfolding / Q000187:drug effects
chemical_list: D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D011328:Prions; C082632:prion protein (106-126)