Intrinsic nucleic acid dynamics modulates HIV-1 nucleocapsid protein binding to its targets.
Intrinsic nucleic acid dynamics modulates HIV-1 nucleocapsid protein binding to its targets.
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DOI：
10.1371/journal.pone.0038905
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Mauffret O
中科院分区：
文献类型：
--
作者：
Bazzi A;Zargarian L;Chaminade F;De Rocquigny H;René B;Mély Y;Fossé P;Mauffret O
HIV-1核衣壳蛋白（NC）参与了逆转录关键步骤中核酸的重排。这种蛋白通过它的两个锌指，优先与单链序列中未配对的鸟嘌呤相互作用。在与HIV-1基因组转激活应答元件cDNA拷贝上半部分相对应的mini-cTAR茎环中，NC对mini-cTAR茎底部的TGG序列表现出明显的偏好。为了进一步了解该位点是如何在含有未配对鸟嘌呤的几个潜在结合位点中被选择的，我们使用13C弛豫测量方法探索了mini-cTAR的内在动力学。自旋弛豫时间的测量结果采用无模型形式进行分析，并由色散弛豫测量完成。我们的数据表明，优先识别的鸟嘌呤在茎的下部是免构象交换和高流动性。相比之下，mini-cTAR中未被识别的未配对鸟嘌呤参与构象交换，可能与瞬时碱基对有关。这些发现支持了NC优先识别表现出高度流动性的未配对鸟嘌呤的观点。NC通过其动态特性区分接近序列的能力有助于理解NC如何识别HIV基因组中的特定位点。
HIV-1 nucleocapsid protein (NC) is involved in the rearrangement of nucleic acids occurring in key steps of reverse transcription. The protein, through its two zinc fingers, interacts preferentially with unpaired guanines in single-stranded sequences. In mini-cTAR stem-loop, which corresponds to the top half of the cDNA copy of the transactivation response element of the HIV-1 genome, NC was found to exhibit a clear preference for the TGG sequence at the bottom of mini-cTAR stem. To further understand how this site was selected among several potential binding sites containing unpaired guanines, we probed the intrinsic dynamics of mini-cTAR using 13C relaxation measurements. Results of spin relaxation time measurements have been analyzed using the model-free formalism and completed by dispersion relaxation measurements. Our data indicate that the preferentially recognized guanine in the lower part of the stem is exempt of conformational exchange and highly mobile. In contrast, the unrecognized unpaired guanines of mini-cTAR are involved in conformational exchange, probably related to transient base-pairs. These findings support the notion that NC preferentially recognizes unpaired guanines exhibiting a high degree of mobility. The ability of NC to discriminate between close sequences through their dynamic properties contributes to understanding how NC recognizes specific sites within the HIV genome.
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