Effect of different arginine methylations on the thermodynamics of Tat peptide binding to HIV-1 TAR RNA
Effect of different arginine methylations on the thermodynamics of Tat peptide binding to HIV-1 TAR RNA
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DOI：
10.1016/j.biochi.2013.03.008
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发表时间：
2013-07-01
期刊：
影响因子：
3.9
通讯作者：
Maiti, Souvik
中科院分区：
文献类型：
--
作者：
Kumar, Santosh;Maiti, Souvik
rna结合蛋白是一类重要的调节细胞功能和分化的介质。精氨酸的甲基化，在这些蛋白质中发现的翻译后修饰（PTM），可以调节它们的功能。精氨酸可以单甲基化或二甲基化，这取决于所涉及的甲基转移酶的类型。本文描述了未修饰和修饰Tat肽与TAR RNA相互作用的热力学比较研究，其中肽在精氨酸侧链第52或53位的胍基的epsilon （epsilon）和eta （eta）氮原子上甲基化。结果表明，精氨酸在epsilon （epsilon）氮原子上的单甲基化提高了结合亲和力，这是由于更有利的焓组分覆盖了不利的熵变化。相比之下，精氨酸残基的单甲基化导致结合亲和力降低，这完全是由不太有利的焓变引起的，而熵组分不受影响。然而，在epsilon和eta位置同时甲基化的情况下，与未修饰的肽相比，结合参数几乎不受影响。在eta位置对称二甲基化的情况下，观察到的结合焓变小于未修饰肽的值。在eta位置的不对称二甲基化由于不太有利的焓变而显示出最低的结合亲和力。这些结果为阐明精氨酸甲基化作为调节蛋白质功能的PTMs的生物学结果提供了见解，并将有助于我们了解这些PTMs是如何在体外和体内建立的。(C) 2013 Elsevier Masson SAS。版权所有。
RNA-binding proteins are an important class of mediators that regulate cell function and differentiation. Methylation of arginine, a post-translational modification (PTM) found in these proteins, can modulate their function. Arginine can be monomethylated or dimethylated, depending on the type of methyl transferases involved. This paper describes a comparative study of the thermodynamics of unmodified and modified Tat peptide interaction with TAR RNA, where the peptide is methylated at epsilon (epsilon) and eta (eta) nitrogen atoms of guanidinium group of arginine side chain at position 52 or 53. The results indicate that monomethylation of arginine at epsilon (epsilon) nitrogen atom enhances binding affinity, owing to a more favourable enthalpy component which overrides the less favourable entropy change. In contrast, monomethylation of arginine residue at eta nitrogen results in reduced binding affinity originating exclusively from a less favourable enthalpy change leaving entropic component unaffected. However, in case of simultaneous methylation at epsilon and eta positions, the binding parameters remain almost unaffected, when compared to the unmodified peptide. In case of symmetric dimethylation at eta position the observed enthalpy change of the binding was found to be smaller than the values obtained for the unmodified peptide. Asymmetric dimethylation at eta position showed the most reduced binding affinities owing to less favourable enthalpy changes. These results provide insights that enable elucidation of the biological outcome of arginine methylation as PTMs that regulate protein function, and will contribute to our understanding of how these PTMs are established in vitro and in vivo. (C) 2013 Elsevier Masson SAS. All rights reserved.