NR AKFY
AU Rudd,P.M.; Endo,T.; Colominas,C.; Groth,D.; Wheeler,S.F.; Harvey,D.J.; Wormald,M.R.; Serban,H.; Prusiner,S.B.; Kobata,A.; Dwek,R.A.
TI Glycosylation differences between the normal and pathogenic prion protein isoforms
QU Proceedings of the National Academy of Sciences of the United States of America 1999 Nov 9; 96(23): 13044-9
PT journal article
AB 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 (PrPc) and pathogenic (PrPsc) 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 PrPc into PrPsc is not confined to a subset of PrPs that contain specific sugars. Compared with PrPc, PrPsc 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 PrPc in cells where PrPsc is formed and argues that, in at least some cells forming PrPsc, 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.
MH Animal; Chromatography, High Pressure Liquid; Glycosylation; Hamsters; Mesocricetus; Models, Molecular; PrP 27-30 Protein/isolation & purification/*metabolism; Protein Isoforms/isolation & purification/*metabolism; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Support, Non-U.S. Gov't
AD Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, United Kingdom.
SP englisch
PO USA