Combined Mechanism of Conformational Selection and Induced Fit in U1A-RNA Molecular Recognition
Combined Mechanism of Conformational Selection and Induced Fit in U1A-RNA Molecular Recognition
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DOI：
10.1021/bi401708q
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发表时间：
2014-06-10
期刊：
影响因子：
2.9
通讯作者：
Nagaoka, Masataka
中科院分区：
文献类型：
--
作者：
Kurisaki, Ikuo;Takayanagi, Masayoshi;Nagaoka, Masataka
在这项研究中，我们表明，U1 A-RNA分子识别介导的构象选择和诱导适合的组合机制。U1 A与RNA的结合已经在诱导拟合的背景下进行了讨论，该诱导拟合涉及U1 A的C-末端区域（Helix-C）中的α-螺旋的重新取向，以仅当U1 A正确识别RNA时才允许RNA进入。然而，根据我们的分子动力学模拟，即使在没有RNA的情况下，Helix-C也会自发地重新定向以允许RNA进入。然而，这种构象变化仍然是不完全的。Helix-C通常是部分甚至完全展开的，并且处于罕见的RNA可接近构象，这可以使用最先进的核磁共振方法检测。这些结果表明，能量稳定的复合物的形成是由U1 A和RNA之间的特异性相互作用促进的。总之，在识别RNA的U1 A蛋白，我们提出了一个组合的机制，需要重新定位的螺旋-C和随后的接触RNA通过构象选择，虽然U1 A RNA复合物的稳定是由诱导适合。我们进一步提出了一个关于U1 A RNA分子识别机制的传统假设的修改。
In this study, we demonstrate that U1A-RNA molecular recognition is mediated by a combined mechanism of conformational selection and induced fit. The binding of U1A to RNA has been discussed in the context of induced fit that involves the reorientation of the alpha-helix in the C-terminal region (Helix-C) of U1A to permit RNA access only when U1A correctly recognizes RNA. However, according to our molecular dynamics simulations, even in the absence of RNA, Helix-C spontaneously reoriented to permit RNA access. Nonetheless, such a conformational change was still incomplete. Helix-C was often partially or even fully unfolded and in an infrequent RNA-accessible conformation, which can be detected using state-of-the-art nuclear magnetic resonance methodology. These results suggest that the formation of an energetically stabilized complex is promoted by specific interactions between U1A and RNA. In conclusion, in the recognition of RNA by U1A protein, we propose a combined mechanism that requires the reorientation of Helix-C and the subsequent contact with RNA through conformational selection, although the stabilization of the U1A RNA complex is caused by induced fit. We further propose a modification to the conventional assumption regarding the mechanism of U1A RNA molecular recognition.