Oxidation of methionine residues in the prion protein by hydrogen peroxide
Oxidation of methionine residues in the prion protein by hydrogen peroxide
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DOI：
10.1016/j.abb.2004.09.012
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发表时间：
2004-12-15
影响因子：
3.9
通讯作者：
Levine, RL
中科院分区：
文献类型：
--
作者：
Requena, JR;Dimitrova, MN;Levine, RL
H2 O2与重组SHa（29-231）朊病毒蛋白反应导致多个蛋氨酸残基的快速氧化。在用溴化氰和lysC消化后通过质谱法评估的单个残留物对氧化的敏感性一般是溶剂暴露的函数。位于PrP（106-126）氨基末端的Met 109和Met 112对PrP的敏感性最高。Met 129是位于人PrP中多态性位置并调节朊病毒疾病风险的残基，也容易氧化，Met 134也是如此。用圆二色谱法研究了H2 O2诱导蛋氨酸氧化对PrP结构的影响。与导致PrP广泛聚集的铜催化氧化相反，该反应仅导致β-折叠结构的适度增加。PrP中暴露于溶剂的甲硫氨酸残基的数量很高，表明它们可能作为保护性内源性抗氧化剂发挥作用。(C)2004爱思唯尔公司All rights reserved.
Reaction of H2O2 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 H2O2-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. (C) 2004 Elsevier Inc. All rights reserved.