Modulation of potassium channel function by methionine oxidation and reduction
Modulation of potassium channel function by methionine oxidation and reduction
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DOI：
10.1073/pnas.94.18.9932
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发表时间：
1997-09-02
影响因子：
11.1
通讯作者：
Hoshi, T
中科院分区：
文献类型：
--
作者：
Ciorba, MA;Heinemann, SH;Hoshi, T
蛋白质中氨基酸残基的氧化可由细胞正常产生的多种氧化剂引起。蛋白质中的甲硫氨酸氧化成甲硫氨酸亚砜与衰老以及病理条件有关，并且它是由普遍存在的酶肽甲硫氨酸亚砜还原酶介导的可逆反应。蛋氨酸氧化的可逆性表明，它可能作为一种细胞调节机制，虽然没有这样的体内活性已被证明。我们在这里表明，在电压依赖性钾通道中的甲硫氨酸残基的氧化调节其失活。当该蛋氨酸残基被氧化为蛋氨酸亚砜时，失活被破坏，并且通过与肽蛋氨酸亚砜还原酶共表达而逆转。结果表明，蛋氨酸的氧化和还原在多种系统的细胞信号转导过程中起着动态的作用。
Oxidation of amino acid residues in proteins can be caused by a variety of oxidizing agents normally produced by cells. The oxidation of methionine in proteins to methionine sulfoxide is implicated in aging as well as in pathological conditions, and it is a reversible reaction mediated by a ubiquitous enzyme, peptide methionine sulfoxide reductase. The reversibility of methionine oxidation suggests that it could act as a cellular regulatory mechanism although no such in vivo activity has been demonstrated. We show here that oxidation of a methionine residue in a voltage-dependent potassium channel modulates its inactivation. When this methionine residue is oxidized to methionine sulfoxide, the inactivation is disrupted, and it is reversed by coexpression with peptide methionine sulfoxide reductase. The results suggest that oxidation and reduction of methionine could play a dynamic role in the cellular signal transduction process in a variety of systems.