Assessing the role of oxidized methionine at position 213 in the formation of prions in hamsters.
Prions are infectious proteins that are able to recruit a normal cellular prion protein and convert it into a prion. The mechanism of this conversion is unknown. Detailed analysis of the normal cellular prion protein and a corresponding prion has shown they possess identical post-translational modifications and differ solely in conformation. Recent work has suggested that the oxidized form of the methionine at position 213 (Met213) plays a role in the conversion of the normal cellular prion protein to the prion conformation and is a prion-specific covalent signature. We developed a sensitive method of quantitating the methionine sulfoxide present at position 213 (MetSO213) and used this method to measure the changes in MetSO213 over the time course of an intracranial challenge, using the 263K strain of hamster-adapted scrapie. These results indicate that the proportion of Met213 that is oxidized decreases over the course of the disease. We examined the quantity of MetSO213 in PrP(C) and compared it to the amount found in animals terminally afflicted with the 263K, 139H, and drowsy strains of hamster-adapted scrapie. These strains show only low levels of MetSO213 that is comparable to that of PrP(C). These data suggest that MetSO213 does not appear to be a prion-specific covalent signature.
Silva
Christopher J
CJ
Western Regional Research Center, United States Department of Agriculture, Albany, California 94710, USA. christopher.silva@ars.usda.gov
Onisko
Bruce C
BC
Dynin
Irina
I
Erickson
Melissa L
ML
Vensel
William H
WH
Requena
Jesús R
JR
Antaki
Elizabeth M
EM
Carter
John Mark
JM
D000595:Amino Acid Sequence; D000818:Animals; D002853:Chromatography, Liquid; D006224:Cricetinae; D005260:Female; D008647:Mesocricetus; D008715:Methionine / Q000031:analogs & derivatives / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D018621:PrPC Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism; D013552:Swine; D053719:Tandem Mass Spectrometry; D014357:Trypsin / Q000737:chemistry
D010446:Peptide Fragments; D018621:PrPC Proteins; D008715:Methionine; D014357:Trypsin; C013111:methionine sulfoxide