Reaction of H(2)O(2) with the recombinant SHa(29-231) prion protein resulted in rapid oxidation of multiple methionine residues. Susceptibility to oxidation of individual residues, assessed by mass spectrometry after digestion with CNBr and lysC, was in general a function of solvent exposure. Met 109 and Met 112, situated in the highly flexible amino terminus, and key residues of the toxic peptide PrP (106-126), showed the greatest susceptibility. Met 129, a residue located in a polymorphic position in human PrP and modulating risk of prion disease, was also easily oxidized, as was Met 134. The structural effect of H(2)O(2)-induced methionine oxidation on PrP was studied by CD spectroscopy. As opposed to copper catalyzed oxidation, which results in extensive aggregation of PrP, this reaction led only to a modest increase in beta-sheet structure. The high number of solvent exposed methionine residues in PrP suggests their possible role as protective endogenous antioxidants.
|Titolo:||Oxidation of methionine residues in the prion protein by hydrogen peroxide|
|Autori:||Requena, J. R.; Dimitrova, M. N.; Legname, G.; Teijeira, S.; Prusiner, S. B.; Levine, R. L.|
|Data di pubblicazione:||2004|
|Digital Object Identifier (DOI):||10.1016/j.abb.2004.09.012|
|Fulltext via DOI:||https://doi.org/10.1016/j.abb.2004.09.012|
|Appare nelle tipologie:||1.1 Journal article|