title: Probing structural differences in prion protein isoforms by tyrosine nitration.
abstract: Two conformational isomers of recombinant hamster prion protein (residues 90-232) have been probed by reaction with two tyrosine nitration reagents, peroxynitrite and tetranitromethane. Two conserved tyrosine residues (tyrosines 149 and 150) are not labeled by either reagent in the normal cellular form of the prion protein. These residues become reactive after the protein has been converted to the beta-oligomeric isoform, which is used as a model of the fibrillar form that causes disease. After conversion, a decrease in reactivity is noted for two other conserved residues, tyrosine 225 and tyrosine 226, whereas little to no effect was observed for other tyrosines. Thus, tyrosine nitration has identified two specific regions of the normal prion protein isoform that undergo a change in chemical environment upon conversion to a structure that is enriched in beta-sheet.
authors.affiliation: Division of Biological Sciences and the Biomolecular Structure and Dynamics Program, The University of Montana, Missoula, Montana 59812, USA.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Lennon
authors.forename: Holly D
authors.initials: HD
authors.lastname: Cox
authors.forename: Scott P
authors.initials: SP
authors.lastname: Hennelly
authors.forename: Sam J
authors.initials: SJ
authors.lastname: Chelmo
authors.forename: Michele A
authors.initials: MA
authors.lastname: McGuirl
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D006224:Cricetinae; D006358:Hot Temperature; D008647:Mesocricetus; D030421:Peroxynitrous Acid / Q000737:chemistry; D018621:PrPC Proteins / Q000737:chemistry; D011328:Prions / Q000737:chemistry*; D011489:Protein Denaturation; D020033:Protein Isoforms / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D013774:Tetranitromethane / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D018621:PrPC Proteins; D011328:Prions; D020033:Protein Isoforms; D030421:Peroxynitrous Acid; D014443:Tyrosine; D013774:Tetranitromethane