Rewiring translation for elongation factor Tu-dependent selenocysteine incorporation.
Rewiring translation for elongation factor Tu-dependent selenocysteine incorporation.
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DOI：
10.1002/anie.201207567
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发表时间：
2013-01-28
影响因子：
16.6
通讯作者：
Soell, Dieter
中科院分区：
文献类型：
--
作者：
Aldag, Caroline;Broecker, Markus J.;Hohn, Michael J.;Prat, Laure;Hammond, Gifty;Plummer, Abigail;Soell, Dieter
硒是动物必需的微量营养素。[1]人类含有25种可能是必需的硒蛋白[2]，其中的硒以硒半胱氨酸(Sec)的形式存在。[3]在这21种遗传编码的氨基酸中，半胱氨酸的硫醇部分被硒醇基取代。在所有SEC解码生物中，SEC的生物合成(方案1B)始于tRNASec被Seryl-tRNA合成酶(SerRS)酰化形成SertRNASec(见参考文献[5])。在细菌中，SertRNASec到Sec-tRNASec的转换是通过硒半胱氨酸合成酶(SELA；在参考文献[4]中综述)实现的。相比之下，古生菌和真核生物采用了额外的磷酸化步骤。O-磷酸丝氨酰-tRNASec激酶(PSTK)使Ser-tRNASec的tRNA结合的Ser部分磷酸化，形成O-磷酸丝氨酰-tRNASec(Sep-tRNASec)，是SepSecs的底物，催化依赖tRNA的Sep到Sec的转化。在硒蛋白合成过程中，SEC被重新编程的UGA终止密码子共翻译结合。一个特殊的延伸因子(细菌中的SELB)和一个位于细菌开放阅读框架(ORF)序列中的RNA结构信号(SECIS元件)是明确停止到SEC记录所必需的。[4]EF-Tu不识别SEC-tRNASec，也歧视SertRNASec。[4]硒和硫在元素周期表中属于同一组元素，并具有某些性质(例如，大小、电负性、主要氧化态)；然而，Cys和SEC通过不同的电极电位、[8]亲核性(Cys和lt；Sec)，[9]和侧链PKA(Cys为8.3，Sec为5.2)。[10]因此，硒蛋白具有独特的性质。[11]Sec经常存在于酶的活性部位，赋予这些蛋白质(例如，氧化还原酶)优异的催化活性。硒酶中Sec到Cys的替换可能导致10到1000倍的活性损失(见参考文献[11B])。虽然二硫键经常出现在蛋白质中以增加稳定性或提供氧化还原功能，但二硒醚的出现频率要低得多。[12]二硒醚在蛋白质中的出现具有令人兴奋的生物学和生物医学意义，因为它们比二硫键[13]更稳定，有时甚至不被DTT还原。[12]这些与SEC相关的性质表明，在蛋白质中包含SEC可以用于设计用于各种应用的蛋白质(例如，X射线结晶学、PET研究、蛋白质折叠、核磁共振光谱、电子顺磁共振光谱)。[14]目前有几种方法可以生产硒蛋白。首先，大肠杆菌SEC插入机制可以用于异源过表达硒蛋白，[15]但它的使用受到SECIS序列限制的严重限制，SECIS序列限制了SEC对任何氨基酸的简单定点替换。哺乳动物的SEC插入似乎更容易一些。[16]第二，固相化学合成SEC-
Selenium is an essential micronutrient for animals.[1] Humans contain 25 presumably essential selenoproteins [2] in which selenium is found in the form of selenocysteine (Sec).[3] In this 21st genetically encoded amino acid [4] the thiol moiety of Cys is replaced by a selenol group. In all Sec-decoding organisms, Sec biosynthesis (Scheme 1B) starts with the acylation of tRNASec by seryl-tRNA synthetase (SerRS) to form SertRNASec (reviewed in Ref.[5]). In bacteria, conversion of SertRNASec to Sec-tRNASec is achieved by selenocysteine synthase (SelA; reviewed in Ref.[4]). In contrast, archaea and eukaryotes employ an additional phosphorylation step. O-phosphoseryl-tRNASec kinase (PSTK) phosphorylates the tRNA-bound Ser moiety of Ser-tRNASec to form O-phosphoseryl-tRNASec (Sep-tRNASec),[6] the substrate for SepSecS that catalyzes the tRNA-dependent Sep to Sec conversion.[7] The selenium donor for both SelA and SepSecS is selenophosphate (reviewed in Refs.[4, 7b]). During selenoprotein synthesis, Sec is co-translationally incorporated by a re-programmed UGA stop codon. A specialized elongation factor (SelB in bacteria) and an RNA structural signal (SECIS element) located within the bacterial open reading frame (ORF) sequence are required for unambiguous Stop to Sec recoding.[4] EF-Tu does not recognize Sec-tRNASec and also discriminates against SertRNASec.[4]Selenium and sulfur are in the same group of elements in the periodic table and share certain properties (eg, size, electronegativity, major oxidation states); yet, Cys and Sec are distinguished by different electrode potentials,[8] nucleophilicity (Cys< Sec),[9] and side-chain pKa (8.3 for Cys versus 5.2 for Sec).[10] Thus, selenoproteins have unique properties.[11] Sec is frequently found in the active sites of enzymes, endowing these proteins (eg, redox enzymes) with superior catalytic activities. Sec to Cys replacements in selenoenzymes may lead to 10 to 1000-fold activity loss (reviewed in Ref.[11b]). Although disulfides occur frequently in proteins to increase stability or provide redox functions, diselenides are much less frequent.[12] The occurrence of diselenides in proteins has exciting biological and biomedical significance, because they are more stable than disulfides [13] and sometimes even resistant to reduction by DTT.[12] These Sec-dependent properties indicate that inclusion of Sec in proteins could be useful in designing proteins for various applications (eg, X-ray crystallography, PET studies, protein folding, NMR spectroscopy, electron paramagnetic resonance spectroscopy).[14] There are currently several strategies to produce selenoproteins. First, the E. coli Sec insertion machinery can be exploited for heterologous overexpression of selenoproteins,[15] but its use is severely limited by sequence constraints of the SECIS sequence, which inhibits facile site-directed replacement of any amino acid with Sec. Mammalian Sec insertion appears to be somewhat easier.[16] Second, solid-phase chemical synthesis of Sec-
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影响因子：
56.9
作者：
DAWSON, PE;MUIR, TW;KENT, SBH
通讯作者：
KENT, SBH
影响因子：
56.9
作者：
Kryukov, GV;Castellano, S;Gladyshev, VN
通讯作者：
Gladyshev, VN
DOI：
10.1073/pnas.73.8.2659
发表时间：
1976-01-01
影响因子：
11.1
作者：
CONE, JE;MARTINDELRIO, R;STADTMAN, TC
通讯作者：
STADTMAN, TC
DOI：
10.1073/pnas.0610683104
发表时间：
2007-05-08
影响因子：
11.1
作者：
Novoselov, Sergey V.;Lobanov, Alexey V.;Gladyshev, Vadim N.
通讯作者：
Gladyshev, Vadim N.
DOI：
10.1126/science.1207203
发表时间：
2011-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Park HS;Hohn MJ;Umehara T;Guo LT;Osborne EM;Benner J;Noren CJ;Rinehart J;Söll D
通讯作者：
Söll D