A critical base pair in k-turns determines the conformational class adopted, and correlates with biological function.

A critical base pair in k-turns determines the conformational class adopted, and correlates with biological function.
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DOI:
10.1093/nar/gkw201
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发表时间:
2016-06-20
影响因子:
14.9
通讯作者:
Lilley DM
Lilley DM
中科院分区:
生物学2区
文献类型:
--
作者:
Huang L;Wang J;Lilley DM

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k转角是常见的基序,其将尖锐的扭结引入双链体RNA中,从而促进三级接触。k-转角的折叠和构象都由其局部序列决定。k-转角分为两种构象类别,称为N3和N1,其在核心中的氢键模式不同。我们在这里表明,这是由与关键G·A对相邻的碱基对决定的。我们确定了一系列KT-7变体的晶体结构,其中3b,3 n位置已经系统地变化,表明这导致构象的转换。我们之前已经表明,3b,3 n位置也决定了k-转角的折叠特性,即k-转角是否可以在单独存在金属离子的情况下折叠。我们分析了核糖体,核糖开关和U4 snRNA的四类k-turn的3b,3 n序列的分布,发现一个给定的k-turn类型的性质的强保守性。因此,我们证明了生物功能,3b,3 n序列和k-转角折叠和构象之间的强关联。这具有很强的预测能力,可以应用于大型RNA结构的建模。
k-turns are commonly-occurring motifs that introduce sharp kinks into duplex RNA, thereby facilitating tertiary contacts. Both the folding and conformation of k-turns are determined by their local sequence. k-turns fall into two conformational classes, called N3 and N1, that differ in the pattern of hydrogen bonding in the core. We show here that this is determined by the basepair adjacent to the critical G•A pairs. We determined crystal structures of a series of Kt-7 variants in which this 3b,3n position has been systematically varied, showing that this leads to a switch in the conformation. We have previously shown that the 3b,3n position also determines the folding characteristics of the k-turn, i.e. whether or not the k-turn can fold in the presence of metal ions alone. We have analyzed the distribution of 3b,3n sequences from four classes of k-turns from ribosomes, riboswitches and U4 snRNA, finding a strong conservation of properties for a given k-turn type. We thus demonstrate a strong association between biological function, 3b,3n sequence and k-turn folding and conformation. This has strong predictive power, and can be applied to the modeling of large RNA architectures.