Further characterization of glycoform-selective prions of variably protease-sensitive prionopathy

Weiguanliu Zhang, Xiangzhu Xiao, Mingxuan Ding, Jue Yuan, Aaron Foutz, Mohammed Moudjou, Tetsuyuki Kitamoto, Jan P.M. Langeveld, Li Cui, Wen Quan Zou

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Prion is an infectious protein (PrPSc ) that is derived from a cellular glycoprotein (PrPC ) through a conformational transition and associated with a group of prion diseases in animals and humans. Characterization of proteinase K (PK)-resistant PrPSc by western blotting has been critical to diagnosis and understanding of prion diseases including Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker (GSS) disease in humans. However, formation as well as biochemical and biological properties of the glycoform-selective PrPSc in variably protease-sensitive prionopathy (VPSPr) remain poorly understood. Here we reveal that formation of the ladder-like PrPSc in VPSPr is a PK-dependent two-step process, which is enhanced by basic pH. Two sets of PrPSc fragments can be identified with antibodies directed against an intermediate or a C-terminal domain of the protein. Moreover, antibodies directed against specific PrP glycoforms reveal faster electrophoretic migrations of PrP fragments mono-glycosylated at residue 181 and 197 in VPSPr than those in sporadic CJD (sCJD). Finally, RT-QuIC assay indicates that PrPSc-seeding activity is lower and its lag time is longer in VPSPr than in sCJD. Our results suggest that the glycoform-selective PrPSc in VPSPr is associated with altered glycosylation, resulting in different PK-truncation and aggregation seeding activity compared to PrPSc in sCJD.

Original languageEnglish
Article number513
Issue number5
Publication statusPublished - 2021 May


  • Creutzfeldt-Jakob disease (CJD)
  • Gerstmann-Sträussler-Scheinker (GSS)
  • Glycoform-selective prion formation
  • Prions disease
  • Real-time quaking-induced conversion (RT-QuIC) assay
  • Variably protease-sensitive prionopathy (VPSPr)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases


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