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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A proton-coupled dynamic conformational switch in the HIV-1 dimerization initiation site kissing complex
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A proton-coupled dynamic conformational switch in the HIV-1 dimerization initiation site kissing complex

机译：HIV-1二聚化起始位点接吻复合体中的质子耦合动态构象转换

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摘要

In HIV type 1 (HIV-1), the dimerization initiation site (DIS) is the sequence primarily responsible for initiating the noncovalent linkage of two homologous strands of genomic RNA during viral assembly. The DIS loop contains an autocomplementary hex-anucleotide sequence and forms a symmetric homodimer through a loop-loop kissing interaction. In a structural rearrangement catalyzed by the HIV-1 nucleocapsid protein (NCp7) and suggested to be associated with maturation of the budded viral particle, the DIS converts from a metastable kissing dimer to an extended duplex. Here, we demonstrate that the DIS kissing dimer displays localized conformational dynamics that result from the specific protonation of the N1 base nitrogen of the DIS loop residue A272 at near-physiological pH. The rate of NCp7-catalyzed maturation of the DIS kissing dimer is also shown to directly correlate with the observed proton-coupled conformational dynamics, where NCp7 is found to convert the dynamic A272 protonated state with a faster rate. Taken together, these results reveal a previously undescribed role for base protonation in modulating local RNA structure and demonstrate a mechanism for promoting the chaperone-mediated structural rearrangement of a kinetically trapped RNA conformational state.
机译：在1型HIV（HIV-1）中，二聚化起始位点（DIS）是主要负责在病毒装配过程中起始基因组RNA的两条同源链非共价键的序列。 DIS环包含一个自身互补的六核苷酸序列，并通过一个环-环亲吻相互作用形成一个对称的同二聚体。在由HIV-1核衣壳蛋白（NCp7）催化的结构重排中，暗示其与萌芽的病毒颗粒的成熟有关，DIS从亚稳的接吻二聚体转变为延伸的双链体。在这里，我们证明了DIS接吻二聚体显示了局部构象动力学，这是由于DIS环残基A272的N1碱基氮在接近生理pH值下的特定质子化所致。还显示了NCp7催化的DIS接吻二聚体的成熟速率与观察到的质子偶联构象动力学直接相关，其中发现NCp7可以更快的速率转化动态A272质子化状态。综上所述，这些结果揭示了先前未描述的碱基质子化在调节局部RNA结构中的作用，并证明了用于促进分子伴侣介导的动力学捕获的RNA构象状态的结构重排的机制。

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