Glycosylation differences between the normal and pathogenic prion protein isoforms
| Autor: | Pauline M. Rudd, Tama Endo, Cristina Colominas, Raymond A. Dwek, Stanley B. Prusiner, Susan F. Wheeler, Hana Serban, Mark R. Wormald, David Harvey, Darlene Groth, Akira Kobata |
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| Rok vydání: | 1999 |
| Předmět: |
Models
Molecular Gene isoform Glycan Glycosylation animal diseases chemistry.chemical_compound Cricetinae Animals Protein Isoforms Chromatography High Pressure Liquid chemistry.chemical_classification Multidisciplinary Mesocricetus biology Biological Sciences Oligosaccharide biology.organism_classification PrP 27-30 Protein nervous system diseases Enzyme chemistry Biochemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization biology.protein Glycoprotein |
| Zdroj: | Proceedings of the National Academy of Sciences. 96:13044-13049 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Prion protein consists of an ensemble of glycosylated variants or glycoforms. The enzymes that direct oligosaccharide processing, and hence control the glycan profile for any given glycoprotein, are often exquisitely sensitive to other events taking place within the cell in which the glycoprotein is expressed. Alterations in the populations of sugars attached to proteins can reflect changes caused, for example, by developmental processes or by disease. Here we report that normal (PrP C ) and pathogenic (PrP Sc ) prion proteins (PrP) from Syrian hamsters contain the same set of at least 52 bi-, tri-, and tetraantennary N-linked oligosaccharides, although the relative proportions of individual glycans differ. This conservation of structure suggests that the conversion of PrP C into PrP Sc is not confined to a subset of PrPs that contain specific sugars. Compared with PrP C , PrP Sc contains decreased levels of glycans with bisecting GlcNAc residues and increased levels of tri- and tetraantennary sugars. This change is consistent with a decrease in the activity of N -acetylglucosaminyltransferase III (GnTIII) toward PrP C in cells where PrP Sc is formed and argues that, in at least some cells forming PrP Sc , the glycosylation machinery has been perturbed. The reduction in GnTIII activity is intriguing both with respect to the pathogenesis of the prion disease and the replication pathway for prions. |
| Databáze: | OpenAIRE |
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