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首页> 外文期刊>Biochemistry >SelT,SelW,SelH,and Rdxl2:Genomics and Molecular Insights into the Functions of Selenoproteins of a Novel Thioredoxin-like Family
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SelT,SelW,SelH,and Rdxl2:Genomics and Molecular Insights into the Functions of Selenoproteins of a Novel Thioredoxin-like Family

机译：SelT，SelW，SelH和Rdxl2：新型硫氧还蛋白样家族硒蛋白功能的基因组学和分子洞察

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摘要

Selenium is an essential trace element in many life forms due to its occurrence as a selenocysteine (Sec) residue in selenoproteins.The majority of mammalian selenoproteins,however,have no known function.Herein,we performed extensive sequence similarity searches to define and characterize a new protein family,designated Rdx,that includes mammalian selenoproteins SelW,SelV,SelT and SelH,bacterial SelW-like proteins and cysteine-containing proteins of unknown function in all three domains of life.An additional member of this family is a mammalian cysteine-containing protein,designated Rdx 12,and its fish selenoprotein orthologue.Rdx proteins are proposed to possess a thioredoxin-like fold and a conserved CxxC or CxxU (U is Sec) motif,suggesting a redox function.We cloned and characterized three mammalian members of this family,which showed distinct expression patterns in mouse tissues and different localization patterns in cells transfected with the corresponding GFP fusion proteins.By analogy to thioredoxin,Rdx proteins can use catalytic cysteine (or Sec) to form transient mixed disulfides with substrate proteins.We employed this property to identify cellular targets of Rdx proteins using affinity columns containing mutant versions of these proteins.Rdx 12 was found to interact with glutathione peroxidase 1,whereas 14-3-3 protein was identified as one of the targets of mammalian SelW,suggesting a mechanism for redox regulation of the 14-3-3 family of proteins.
机译：硒由于在硒蛋白中作为硒代半胱氨酸（Sec）残基而存在，因此在许多生命形式中都是必不可少的微量元素。然而，大多数哺乳动物硒蛋白尚无已知功能。在此，我们进行了广泛的序列相似性搜索以定义和表征一个新的蛋白质家族，命名为Rdx，包括哺乳动物的硒蛋白SelW，SelV，SelT和SelH，在生活的所有三个域中功能未知的细菌类SelW蛋白和含半胱氨酸的蛋白。该家族的另一个成员是哺乳动物半胱氨酸含有Rdx 12的蛋白质及其鱼类硒蛋白直向同源物。Rdx蛋白质拟具有硫氧还蛋白样折叠，并具有保守的CxxC或CxxU（U is Sec）基序，暗示其氧化还原功能。我们克隆并鉴定了三个哺乳动物成员该家族在小鼠组织中表现出不同的表达模式，并在用相应的GFP融合蛋白转染的细胞中表现出不同的定位模式。与硫氧还蛋白相似，Rdx蛋白可以使用催化半胱氨酸（或Sec）与底物蛋白形成短暂的混合二硫化物。我们利用此特性通过包含这些蛋白突变型的亲和柱鉴定了Rdx蛋白的细胞靶标。发现Rdx 12相互作用谷胱甘肽过氧化物酶1，而14-3-3蛋白被确定为哺乳动物SelW的目标之一，建议对14-3-3蛋白家族的氧化还原调节的机制。

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