The linkage between magnesium binding and RNA folding
The linkage between magnesium binding and RNA folding
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DOI：
10.1006/jmbi.2002.5422
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发表时间：
2002-04-05
影响因子：
5.6
通讯作者：
Draper, DE
中科院分区：
文献类型：
--
作者：
Misra, VK;Draper, DE
理解Mg 2+结合和RNA折叠之间的联系需要一个适当的理论模型来描述Mg 2+结合RNA的折叠和未折叠状态的能量学。我们目前对Mg 2+与这些不同RNA状态结合的理解来自经验热力学模型，该模型依赖于一些不合理的假设。我们提出了一个严格的理论模型，描述RNA折叠和镁离子结合之间的联系。在该模型中，基于非线性Poisson-Boltzmann（NLPB）方程，Mg 2+对RNA的稳定作用来自两种不同的结合模式，扩散结合和位点结合。扩散结合的Mg 2+被描述为被吸引到RNA的负电荷的水合离子的集合。位点结合的Mg 2+是部分去溶剂化的离子，其被吸引到RNA表面上的电负性口袋。我们探索两个系统，酵母tRNA（苯丙氨酸）和58个核苷酸的rRNA片段，具有不同的Mg 2+结合特性。NLPB方程准确地描述了这两个系统的成像之间的化学计量和能量联系，而不需要在计算中的任何拟合参数。此外，NLPB模型提出了一个明确的物理描述如何Mg 2+结合帮助折叠的RNA。对于这里研究的两种分子，相关的未折叠状态是一种无序的中间状态（1），它包含稳定的螺旋二级结构，没有任何三级接触。扩散结合的Mg 2+与这些二级结构元素相互作用以稳定I态。I状态的二级结构元件折叠成紧凑的天然三级结构（N状态）。扩散结合在稳定两种RNA的N态中起着主导作用。然而，对于rRNA片段，与具有非常高的静电势的位置结合的位点也与折叠相关联。我们的研究结果表明，许多实验数据测量Mg 2+结合和RNA折叠之间的联系必须重新解释。(C)2002 Elsevier Science Ltd.
Understanding the linkage between Mg2+ binding and RNA folding requires a proper theoretical model describing the energetics of Mg2+ binding to the folded and unfolded states of RNA. Our current understanding of Mg2+ binding to these different RNA states derives from empirical thermodynamic models that depend on a number of unjustified assumptions. We present a rigorous theoretical model describing the linkage between RNA folding and magnesium ion binding. In this model, based on the non-linear Poisson-Boltzmann (NLPB) equation, the stabilization of RNA by Mg2+ arises from two distinct binding modes, diffuse binding and site binding. Diffusely bound Mg2+ are described as an ensemble of hydrated ions that are attracted to the negative charge of the RNA. Site-bound Mg2+ are partially desolvated ions that are attracted to electronegative pockets on the RNA surface. We explore two systems, yeast tRNA(Phe) and a 58-nucleotide rRNA fragment, with different Mg2+ binding properties. The NLPB equation accurately describes both the stoichiometric and energetic linkage between imaging for both of these systems without requiring any fitted parameters in the calculation. Moreover, the NLPB model presents a well-defined physical description of how Mg2+ binding helps fold an RNA. For both of the molecules studied here, the relevant unfolded state is a disordered intermediate state (1) that contains stable helical secondary structure without any tertiary contacts. Diffusely bound Mg2+ interact with these secondary structure elements to stabilize the I state. The secondary structural elements of the I state fold into a compact, native tertiary structure (the N state). Diffuse binding plays a dominant role in stabilizing the N state for both RNAs studied. However, for the rRNA fragment, site-binding to a location with extraordinarily high electrostatic potential is also coupled to folding. Our results suggest that much experimental data measuring the linkage between Mg2+ binding and RNA folding must be reinterpreted. (C) 2002 Elsevier Science Ltd.