Abstract
Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans. During the course of the disease, the abnormally folded scrapie prion protein (PrPSc) accumulates in the central nervous system where it causes neurodegeneration. In prion disorders, the diverse spectrum of illnesses exists because of the presence of different isoforms of PrPSc where they occupy distinct conformational states called strains. Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP). Characterization of the exact N-glycan structures attached on either PrPC or PrPSc is lacking. Here we report the characterization and comparison of N-glycans from two different sheep prion strains. PrPSc from both strains was isolated from brain tissue and enzymatically digested with trypsin. By using liquid chromatography coupled to electrospray mass spectrometry, a site-specific analysis was performed. A total of 100 structures were detected on both glycosylation sites. The N-glycan profile was shown to be similar to the one on mouse PrP, however, with additional 40 structures reported. The results presented here show no major differences in glycan composition, suggesting that glycans may not be responsible for the differences in the two analyzed prion strains.
Highlights
Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a group of fatal and infectious neurodegenerative diseases
We know it is the abnormal form of the prion protein (PrPSc) that causes the disease, many questions are still left unanswered
Transmissible spongiform encephalopathies (TSEs), are a group of fatal and infectious neurodegenerative diseases. These disorders are characterized by brain inflammation, spongiform degeneration, and accumulation of infectious prion protein denoted as scrapie prion, eventually leading to neuronal death [1,2]
Summary
Transmissible spongiform encephalopathies (TSEs), are a group of fatal and infectious neurodegenerative diseases These disorders are characterized by brain inflammation, spongiform degeneration, and accumulation of infectious prion protein denoted as scrapie prion, eventually leading to neuronal death [1,2]. The two isoforms of the protein have the same primary amino acid sequence, with two N-glycosylation sites (at positions N-184 and N-200 in sheep) preserved in both forms. They differ in their secondary structure–while PrPC is rich in α-helices, PrPSc has a high proportion of β-sheets [3,4]. PrPres (PK-resistant form of PrP) displays characteristic three-band pattern, corresponding to the diglycosylated (where both glycosylation sites are occupied), monoglycosylated (only one of the two sites is occupied), and unglycosylated band [5]
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