Molecular Dynamics Study of the Phosphorylation Effect on the Conformational States of the C-terminal Domain of RNA Polymerase II
Molecular Dynamics Study of the Phosphorylation Effect on the Conformational States of the C-terminal Domain of RNA Polymerase II
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RNA聚合酶II C端结构域磷酸化效应的分子动力学研究
DOI：
10.1021/jp4101976
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Y.Yonezawa
中科院分区：
文献类型：
--
作者：
西田 直哉;大前 英司;楯 真一;Y.Yonezawa
真核生物中RNA聚合酶II的羧基末端结构域（CTD）通过募集各种调控因子来调控mRNA的加工过程。CTD的主要功能依赖于七肽共有序列（YSPTSPS）。CTD动态地改变其构象状态以识别和结合不同的调节因子。动态构象变化是由丝氨酸残基的修饰引起的，主要是磷酸化和去磷酸化。在这项研究中，我们调查的构象状态的单位共识CTD肽的丝氨酸残基的各种磷酸化模式的扩展合奏模拟。结果表明，未磷酸化的CTD具有分布在扭曲和伸展状态之间的柔性无序结构，但磷酸化倾向于缩小构象空间。发现磷酸化诱导磷酸化丝氨酸残基周围的β-转角，脯氨酸残基的顺式构象显著抑制β-转角的形成。β-转角应通过改变构象倾向与诱导拟合相结合来促进不同调节因子的特异性CTD结合。
The carboxyl-terminal domain (CTD) of RNA polymerase II in eukaryotes regulates mRNA processing processes by recruiting various regulation factors. A main function of the CTD relies on the heptad consensus sequence (YSPTSPS). The CTD dynamically changes its conformational state to recognize and bind different regulation factors. The dynamical conformation changes are caused by modifications, mainly phosphorylation and dephosphorylation, to the serine residues. In this study, we investigate the conformational states of the unit consensus CTD peptide with various phosphorylation patterns of the serine residues by extended ensemble simulations. The results show that the CTD without phosphorylation has a flexible disordered structure distributed between twisted and extended states, but phosphorylation tends to reduce the conformational space. It was found that phosphorylation induces a β-turn around the phosphorylated serine residue and the cis conformation of the proline residue significantly inhibits the β-turn formation. The β-turn should contribute to specific CTD binding of the different regulation factors by changing the conformation propensity combined with induced fit.