Charge Density of Cation Determines Inner versus Outer Shell Coordination to Phosphate in RNA
Charge Density of Cation Determines Inner versus Outer Shell Coordination to Phosphate in RNA
复制标题
阳离子的电荷密度决定了 RNA 中磷酸根的内壳与外壳的配位
DOI：
10.1021/acs.jpcb.0c02371
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Thirumalai, D.
中科院分区：
文献类型：
--
作者：
Nguyen, Hung T.;Thirumalai, D.
RNA 折叠通常需要二价阳离子，RNA 是一种高电荷聚阴离子。 RNA 附近的离子（例如 Mg2+ 或 Ca2+）的缩合使磷酸基团上的有效电荷重新正常化，从而最大限度地减少 RNA 内的静电排斥。普遍的观点是二价离子以非特异性方式扩散结合。与此形成鲜明对比的是，我们使用离子与磷酸基团相互作用的理论，使用 RISM 理论并结合基于精确的三相互作用位点 RNA 模型的模拟，得出了完全相反的结论。二价离子利用内壳（部分脱水）或外壳（完全水合）配位以核苷酸特异性方式结合。高电荷密度的 Mg2+ 离子优先与外壳结合，而 Ca2+ 的情况则相反。令人惊讶的是，我们发现桥联相互作用，涉及与两个或多个磷酸基团配位的离子，在维持折叠状态的完整性方面发挥着至关重要的作用。随着 RNA 大小的增加，它们的重要性可能会变得越来越突出。由于二价离子与 DNA 的相互作用模式可能相似，因此我们认为特定的内壳和外壳协调可能在 DNA 凝聚以及基因组组织中发挥作用。
Divalent cations are often required to fold RNA, which is a highly charged polyanion. Condensation of ions, such as Mg2+or Ca2+, in the vicinity of RNA renormalizes the effective charges on the phosphate groups, thus minimizing the intra RNA electrostatic repulsion. The prevailing view is that divalent ions bind diffusively in a nonspecific manner. In sharp contrast, we arrive at the exact opposite conclusion using a theory for the interaction of ions with the phosphate groups using RISM theory in conjunction with simulations based on an accurate three-interaction-site RNA model. The divalent ions bind in a nucleotide-specific manner using either the inner (partially dehydrated) or outer (fully hydrated) shell coordination. The high charge density Mg2+ion has a preference to bind to the outer shell, whereas the opposite is the case for Ca2+. Surprisingly, we find that bridging interactions, involving ions that are coordinated to two or more phosphate groups, play a crucial role in maintaining the integrity of the folded state. Their importance could become increasingly prominent as the size of the RNA increases. Because the modes of interaction of divalent ions with DNA are likely to be similar, we propose that specific inner and outer shell coordination could play a role in DNA condensation, and perhaps genome organization as well.