NR AMGW
AU Weber,D.J.; McFadden,P.N.; Caughey,B.W.
TI Measurement of altered aspartyl residues in the scrapie associated form of prion protein
QU Biochemical and Biophysical Research Communications 1998 May 29; 246(3): 606-8
PT journal article
AB In transmissible spongiform encephalopathies (TSE), the endogenous protease-sensitive prion protein (PrP-sen) of the host is converted to a pathologic form (PrPres) that has greatly enhanced proteinase K resistance, insolubility, and beta sheet content. To investigate the possibility that alterations at aspartyl or asparaginyl residues in the form of D-aspartate and/or L-isoaspartate could play a role in either the formation or stabilization of PrPres in TSE-infected animals, we assayed for the presence of these abnormal residues in PrPres. Protein D-aspartyl/L-isoaspartyl carboxyl methyltransferase (PIMT) was used to methylate and radiolabel altered aspartyl residues, which were detected in PrPres, but at low levels (0.5 mole%). The scarcity of D-aspartyl and/or L-isoaspartyl groups in PrPres suggests that this modification is unlikely to be primarily responsible for the differences between PrPres and PrP-sen. However, it remains possible that such modifications in substoichiometric numbers of PrP molecules could help to initiate the PrPres formation or stabilize PrPres polymers in vivo.
MH Animal; Asparagine/chemistry; Aspartic Acid/*chemistry/metabolism; Hamsters; Isomerism; PrPsc Proteins/*chemistry/metabolism; Protein D-Aspartate-L-Isoaspartate Methyltransferase; Protein Methyltransferases/metabolism; *Protein Processing, Post-Translational; *Scrapie
AD Department of Biochemistry & Biophysics, Oregon State University, Corvallis 97333, USA
SP englisch
PO USA