NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family
NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family
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DOI：
10.1074/jbc.m511386200
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发表时间：
2006-02-10
影响因子：
4.8
通讯作者：
Deisenhofer, J
中科院分区：
文献类型：
--
作者：
Ferguson, AD;Labunskyy, VM;Deisenhofer, J
硒具有显著的健康益处，包括有效的癌症预防活性以及在免疫功能和男性生殖系统中的作用。含硒蛋白质，其中纳入这种必需的微量营养素作为硒代半胱氨酸，提出调解膳食硒的积极作用。这里提出的是硒蛋白SelM和硒蛋白Sep 15的直系同源物的溶液NMR结构。这些数据表明，Sep 15和SelM是结构同源物，建立了一个新的硫氧还蛋白样蛋白家族。折叠内的活性位点氧化还原基序的位置连同硫醇-二硫化物交换和测量的氧化还原电位后观察到的局部构象变化表明它们具有氧化还原活性。在哺乳动物中，Sep 15的表达受膳食硒的调节，并且该硒蛋白的表达的减少或增加改变氧化还原稳态。Sep 15和SelM作为巯基-二硫键氧化还原酶的生理作用及其对内质网质量控制途径的贡献进行了讨论。
Selenium has significant health benefits, including potent cancer prevention activity and roles in immune function and the male reproductive system. Selenium- containing proteins, which incorporate this essential micronutrient as selenocysteine, are proposed to mediate the positive effects of dietary selenium. Presented here are the solution NMR structures of the selenoprotein SelM and an ortholog of the selenoprotein Sep15. These data reveal that Sep15 and SelM are structural homologs that establish a new thioredoxinlike protein family. The location of the active-site redox motifs within the fold together with the observed localized conformational changes after thiol-disulfide exchange and measured redox potential indicate that they have redox activity. In mammals, Sep15 expression is regulated by dietary selenium, and either decreased or increased expression of this selenoprotein alters redox homeostasis. A physiological role for Sep15 and SelM as thiol- disulfide oxidoreductases and their contribution to the quality control pathways of the endoplasmic reticulum are discussed.