首页> 外文期刊>Journal of Molecular Biology >Extended structures in RNA folding intermediates are due to nonnative interactions rather than electrostatic repulsion.
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Extended structures in RNA folding intermediates are due to nonnative interactions rather than electrostatic repulsion.

机译:RNA折叠中间体中的扩展结构是由于非天然相互作用而不是静电排斥引起的。

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RNA folding occurs via a series of transitions between metastable intermediate states for Mg(2+) concentrations below those needed to fold the native structure. In general, these folding intermediates are considerably less compact than their respective native states. Our previous work demonstrates that the major equilibrium intermediate of the 154-residue specificity domain (S-domain) of the Bacillus subtilis RNase P RNA is more extended than its native structure. We now investigate two models with falsifiable predictions regarding the origins of the extended intermediate structures in the S-domains of the B. subtilis and the Escherichia coli RNase P RNA that belong to different classes of P RNA and have distinct native structures. The first model explores the contribution of electrostatic repulsion, while the second model probes specific interactions in the core of the folding intermediate. Using small-angle X-ray scattering and Langevin dynamics simulations, we show that electrostatics plays only a minor role, whereas specific interactions largely account for the extended nature of the intermediate. Structural contacts in the core, including a nonnative base pair, help to stabilize the intermediate conformation. We conclude that RNA folding intermediates adopt extended conformations due to short-range, nonnative interactions rather than generic electrostatic repulsion of helical domains. These principles apply to other ribozymes and riboswitches that undergo functionally relevant conformational changes.
机译:RNA折叠通过Mg(2+)浓度低于折叠天然结构所需浓度的亚稳态中间状态之间的一系列过渡而发生。通常,这些折叠中间体比它们各自的天然状态紧凑得多。我们以前的工作表明枯草芽孢杆菌RNase P RNA的154个残基特异性结构域(S结构域)的主要平衡中间体比其天然结构更广泛地延伸。现在我们调查两个模型,这些模型关于枯草芽孢杆菌和大肠杆菌RNase P RNA的S结构域中扩展中间结构的起源,它们属于不同类的P RNA,并且具有不同的天然结构。第一个模型探究静电排斥的作用,而第二个模型探究折叠中间体的核心中的特定相互作用。使用小角度X射线散射和Langevin动力学模拟,我们显示出静电仅起次要作用,而特定的相互作用很大程度上解释了中间体的扩展性质。核心中的结构接触(包括非本地碱基对)有助于稳定中间构象。我们得出的结论是,RNA折叠中间体由于近距离,非天然相互作用而不是螺旋结构域的通用静电排斥,因此采用了扩展的构象。这些原理适用于经历功能相关构象变化的其他核酶和核糖开关。

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