SelT, SelW, SelH, and Rdx12: Genomics and Molecular Insights into the Functions of Selenoproteins of a Novel Thioredoxin-like Family

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• 作者：Alexander Dikiy ; Sergey V. Novoselov ; Dmitri E. Fomenko ; Aniruddha Sengupta ; Bradley A. Carlson ; Ronald L. Cerny ; Krzysztof Ginalski ; Nick V. Grishin ; Dolph L. Hatfield ; Vadim N. Gladyshev
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：June 12, 2007
• 年：2007
• 卷：46
• 期：23
• 页码：6871 - 6882
• 全文大小：1147K
• 年卷期：v.46,no.23(June 12, 2007)
• ISSN：1520-4995

文摘

Selenium is an essential trace element in many life forms due to its occurrence as aselenocysteine (Sec) residue in selenoproteins. The majority of mammalian selenoproteins, however, haveno known function. Herein, we performed extensive sequence similarity searches to define and characterizea new protein family, designated Rdx, that includes mammalian selenoproteins SelW, SelV, SelT andSelH, bacterial SelW-like proteins and cysteine-containing proteins of unknown function in all three domainsof life. An additional member of this family is a mammalian cysteine-containing protein, designated Rdx12,and its fish selenoprotein orthologue. Rdx proteins are proposed to possess a thioredoxin-like fold and aconserved CxxC or CxxU (U is Sec) motif, suggesting a redox function. We cloned and characterizedthree mammalian members of this family, which showed distinct expression patterns in mouse tissuesand different localization patterns in cells transfected with the corresponding GFP fusion proteins. Byanalogy to thioredoxin, Rdx proteins can use catalytic cysteine (or Sec) to form transient mixed disulfideswith substrate proteins. We employed this property to identify cellular targets of Rdx proteins using affinitycolumns containing mutant versions of these proteins. Rdx12 was found to interact with glutathioneperoxidase 1, whereas 14-3-3 protein was identified as one of the targets of mammalian SelW, suggestinga mechanism for redox regulation of the 14-3-3 family of proteins.