A-Minor Tertiary Interactions in RNA Kink-Turns. Molecular Dynamics and Quantum Chemical Analysis
A-Minor Tertiary Interactions in RNA Kink-Turns. Molecular Dynamics and Quantum Chemical Analysis
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DOI：
10.1021/jp2065584
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发表时间：
2011-12-01
影响因子：
3.3
通讯作者：
Sponer, Jiri
中科院分区：
文献类型：
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作者：
Reblova, Kamila;Sponer, Judit E.;Sponer, Jiri
RNA kink-turn 是一个重要的重复 RNA 基序；具有特征共有序列的内部循环，形成高度保守的三维结构。 RNA 扭结转角的功能排列显示磷酸二酯主链的急剧弯曲。在其他标志性相互作用中，扭结转弯在两个词干之间形成 A 小调相互作用。大多数扭结转角具有扩展的 A 小 I (A-I) 相互作用，其中 NC 茎的第二个 A 中心点 G 碱基对的腺嘌呤通过反式糖边/糖边 (tSS) 和顺式糖边/糖边 (cSS) 相互作用与 C 茎的第一对规范对（即受体对）相互作用。其余的扭结转弯具有不太紧凑的 A 小调 0 (A-0) 相互作用，仅与一个 tSS 接触。我们表明，核糖体 X 射线结构中 A-I 的扭结在进化过程中保留了 G=C 受体碱基对，而反向碱基对 (C=G) 并未实现。相反，在观察到的结构中，A-0 的扭结转角在序列中交替出现 G=C 和 C=G 碱基对。我们进行了一系列扩展（类似于 5 μs）的扭结转弯显式溶剂分子动力学模拟，以合理化这种结构/进化模式。模拟是使用净中性 Na+ 阳离子气氛（阳离子浓度类似于 0.25 M）进行的，并辅以过量盐 KCl 气氛或包含 Mg2+ 的模拟。结果似乎并不依赖于离子处理。模拟从几个扭结转弯的 X 射线结构开始，同时我们测试了模拟系统对碱基替换、适度的结构扰动和约束的响应。模拟中看到的趋势表明，A-I/G=C 排列优于所有其他三种结构。 A-I/C=G 三元组在结构上似乎完全不稳定，与进化过程中看到的共变模式一致。在模拟中，A-0 排列倾向于转向 A-I 模式，这表明 A-0 相互作用的形成可能得到周围蛋白质和 RNA 分子的支持。 A-0 也可以通过不属于扭结转角共有序列的额外扭结转角核苷酸来稳定，如核糖体螺旋 15 的扭结转角所示。对所有四个 A 小三元组的量子化学计算表明，A-I/G=C 和 A-I/C=G 三元组中存在不同的静电和分散稳定性平衡，这可能解释了这些其他等排三元组在扭结转角背景下的不同行为。
The RNA kink-turn is an important recurrent RNA motif; an internal loop with characteristic consensus sequence forming highly conserved three-dimensional structure. Functional arrangement of RNA kink-turns shows a sharp bend in the phosphodiester backbone. Among other signature interactions, kink-turns form A-minor interaction between their two stems. Most kink-turns possess extended A-minor I (A-I) interaction where adenine of the second A center dot G base pair of the NC-stem interacts with the first canonical pair of the C-stem (i.e., the receptor pair) via trans-sugar-edge/sugar-edge (tSS) and cis-sugar-edge/sugar-edge (cSS) interactions. The remaining kink-turns have less compact A-minor 0 (A-0) interaction with just one tSS contact. We show that kink-turns with A-I in ribosomal X-ray structures keep G=C receptor base pair during evolution while the inverted pair (C=G) is not realized. In contrast, kink-turns with A-0 in the observed structures alternate G=C and C=G base pairs in sequences. We carried out an extended set (similar to 5 mu s) of explicit-solvent molecular dynamics simulations of kink-turns to rationalize this structural/evolutionary pattern. The simulations were done using a net-neutral Na+ cation atmosphere (with similar to 0.25 M cation concentration) supplemented by simulations with either excess salt KCl atmosphere or inclusion of Mg2+. The results do not seem to depend on the treatment of ions. The simulations started with X-ray structures of several kink-turns while we tested the response of the simulated system to base substitutions, modest structural perturbations and constraints. The trends seen in the simulations reveal that the A-I/G=C arrangement is preferred over all three other structures. The A-I/C=G triple appears structurally entirely unstable, consistent with the covariation patterns seen during the evolution. The A-0 arrangements tend to shift toward the A-I pattern in simulations, which suggests that formation of the A-0 interaction is likely supported by the surrounding protein and RNA molecules. A-0 may also be stabilized by additional kink-turn nucleotides not belonging to the kink-turn consensus, as shown for the kink-turn from ribosomal Helix 15. Quantum-chemical calculations on all four A-minor triples suggest that there is a different balance of electrostatic and dispersion stabilization in the A-I/G=C and A-I/C=G triples, which may explain different behavior of these otherwise isosteric triples in the context of kink-turns.