Heat shock protein 104 inhibited the fibrillization of prion peptide 106–126 and disassembled prion peptide 106–126 fibrils in vitro
Copyright policy )Heat shock protein 104 inhibited the fibrillization of prion peptide 106–126 and disassembled prion peptide 106–126 fibrils in vitro
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.
- National Institute for Viral Disease Control and Prevention China (People's Republic of)
- Chinese Center For Disease Control and Prevention China (People's Republic of)
- Anhui University of Science and Technology China (People's Republic of)
- State Key Laboratory of Infectious Disease Prevention and Control China (People's Republic of)
Prions, Molecular Sequence Data, Peptide Fragments, Protein Structure, Secondary, Fungal Proteins, Cell Line, Tumor, Humans, Amino Acid Sequence, Protein Multimerization, Heat-Shock Proteins, Protein Unfolding
Prions, Molecular Sequence Data, Peptide Fragments, Protein Structure, Secondary, Fungal Proteins, Cell Line, Tumor, Humans, Amino Acid Sequence, Protein Multimerization, Heat-Shock Proteins, Protein Unfolding
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