Limited understanding of the functional diversity of N-linked glycans as a major gap of prion biology.
Among a broad range of hypotheses on the molecular nature of transmissible spongiform encephalopathy or scrapie agents discussed in 1960s was a hypothesis of self-replicating polysaccharides. While the studies of the past 40 years provided unambiguous proof that this is not the case, emerging evidence suggests that carbohydrates in the form of sialylated N-linked glycans, which are a constitutive part of mammalian prions or PrPSc, are essential in determining prion fate in an organism. The current extra-view article discusses recent advancements on the role of N-linked glycans and specifically their sialylation status in controlling prion fate. In addition, this manuscript introduces a new concept on the important role of strain-specific functional carbohydrate epitopes on the PrPScsurface as main determinants of strain-specific biologic features. According to this concept, individual strain-specific folding patterns of PrPScgovern selection of PrPCsialoglycoforms expressed by a host that can be accommodated within particular PrPScstructures. Strain-specific patterns of functional carbohydrate epitopes formed by N-linked glycans on PrPScsurfaces define strain-specific biologic features. As a constitutive part of PrPSc, the individual strain-specific patterns of carbohydrate epitopes propagate faithfully within a given host as long as individual strain-specific PrPScstructures are maintained, ensuring inheritance of strain-specific biologic features.
a Center for Biomedical Engineering and Technology and Department of Anatomy and Neurobiology , University of Maryland School of Medicine , Baltimore , MD , USA.
Ilia V
IV
Baskakov
D000818:Animals; D002236:Carbohydrate Conformation; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000032:analysis* / Q000378:metabolism; D011134:Polysaccharides / Q000032:analysis* / Q000378:metabolism; D017096:Prion Diseases / Q000378:metabolism*; D000072002:Prion Proteins / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
D011134:Polysaccharides; D000072002:Prion Proteins; D019158:N-Acetylneuraminic Acid
N-linked glycans; carbohydrate epitopes; microglia; prion; prion diseases; secondary lymphoid organs; sialic acid; sialylation