title: Measurement of altered aspartyl residues in the scrapie associated form of prion protein.
abstract: In transmissible spongiform encephalopathies (TSE), the endogenous protease-sensitive prion protein (PrP-sen) of the host is converted to a pathologic form (PrP-res) 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 PrP-res in TSE-infected animals, we assayed for the presence of these abnormal residues in PrP-res. Protein D-aspartyl/L-isoaspartyl carboxyl methyltransferase (PIMT) was used to methylate and radiolabel altered aspartyl residues, which were detected in PrP-res, but at low levels (0.5 mole%). The scarcity of D-aspartyl and/or L-isoaspartyl groups in PrP-res suggests that this modification is unlikely to be primarily responsible for the differences between PrP-res and PrP-sen. However, it remains possible that such modifications in substoichiometric numbers of PrP molecules could help to initiate the PrP-res formation or stabilize PrP-res polymers in vivo.
authors.affiliation: Department of Biochemistry & Biophysics, Oregon State University, Corvallis 97333, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Weber
authors.forename: P N
authors.initials: PN
authors.lastname: McFadden
authors.forename: B
authors.initials: B
authors.lastname: Caughey
mesh_terms: D000818:Animals; D001216:Asparagine / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry* / Q000378:metabolism; D006224:Cricetinae; D007536:Isomerism; D018620:PrPSc Proteins / Q000737:chemistry* / Q000378:metabolism; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase; D011496:Protein Methyltransferases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012608:Scrapie
chemical_list: D018620:PrPSc Proteins; D001224:Aspartic Acid; D001216:Asparagine; D011496:Protein Methyltransferases; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase