Is counterion delocalization responsible for collapse in RNA folding?
Is counterion delocalization responsible for collapse in RNA folding?
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DOI：
10.1021/bi001820r
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发表时间：
2000-11-28
期刊：
影响因子：
2.9
通讯作者：
Rose, GD
中科院分区：
文献类型：
--
作者：
Murthy, VL;Rose, GD
虽然能量和系统发育的方法已经非常成功的预测核酸的二级结构，安排这些二级结构元素到三级结构仍然是一个难题。在这里，我们探索的DNA，RNA和DNA/RNA混合分子在晶体中的包装安排。在传统观点中，高电荷的双螺旋将被有利的溶剂化效应推向孤立;与其他带相同电荷的堆叠的相互作用将非常不利。与此预期相反，我们发现大多数分析的情况下（类似于80%）表现出特定的，优先包装的二级结构的元素之间，其中福尔斯分为三类：（i）联锁的两个螺旋的主要凹槽，（ii）并排平行包装的螺旋，和（iii）放置的核糖磷酸骨架脊的一个螺旋到另一个的主要凹槽。平行包装图案的优势尤其令人惊讶。这一类预计将最大限度地不受欢迎的电荷排斥。相反，它包含超过50%的A型RNA晶体中的所有包装相互作用，并且也在大RNA分子的晶体结构中观察到。为了解释这个难题，我们引入了一个新的RNA折叠模型。一个简单的计算表明，螺旋周围凝聚的阳离子云所获得的熵超过了平行排列的库仑排斥。我们建议，这些凝聚的抗衡离子负责熵驱动的RNA崩溃，类似于蛋白质折叠中的疏水效应的作用。
Although energetic and phylogenetic methods have been very successful for prediction of nucleic acid secondary structures, arrangement of these secondary structure elements into tertiary structure has remained a difficult problem. Here we explore the packing arrangements of DNA, RNA, and DNA/RNA hybrid molecules in crystals. In the conventional view, the highly charged double helix will be pushed toward isolation by favorable solvation effects; interactions with other like-charged stacks would be strongly disfavored. Contrary to this expectation, we find that most of the cases analyzed (similar to 80%) exhibit specific, preferential packing between elements of secondary structure, which falls into three categories: (i) interlocking of major grooves of two helices, (ii) side-by-side parallel packing of helices, and (iii) placement of the ribose-phosphate backbone ridge of one helix into the major groove of another. The preponderance of parallel packing motifs is especially surprising. This category is expected to be maximally disfavored by charge repulsion. Instead, it comprises in excess of 50% of all packing interactions in crystals of A-form RNA and has also been observed in crystal structures of large RNA molecules. To explain this puzzle, we introduce a novel model for RNA folding. A simple calculation suggests that the entropy gained by a cloud of condensed cations surrounding the helices more than offsets the Coulombic repulsion of parallel arrangements. We propose that these condensed counterions are responsible for entropy-driven RNA collapse, analogous to the role of the hydrophobic effect in protein folding.