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CAR生物活性二级结构的动力学组装,HIV-1 Rev蛋白的靶序列。

Kinetic assembling of the biologically active secondary structure for CAR, the target sequence for the Rev protein of HIV-1.

作者信息

Fernández A

机构信息

Department of Chemistry, University of Miami, Coral Gables, Florida 33124.

出版信息

Arch Biochem Biophys. 1990 Aug 1;280(2):421-4. doi: 10.1016/0003-9861(90)90352-y.

DOI:10.1016/0003-9861(90)90352-y
PMID:2195997
Abstract

We predict the metastable secondary structure for the CAR (cis anti-repressor sequence) which is active in the regulation of the interaction with the Rev protein of HIV-1. We prove that the active structure sustained between nts 7364 and 7559 of the env RNA is the most probable metastable structure whose formation is kinetically governed and not thermodynamically determined. The structure is obtained by means of a Monte Carlo simulation which computes refolding events which occur as the CAR portion of the viral RNA is being assembled. Thus, the regulatory role of the secondary structure is determined as soon as the new RNA has been synthesized and it is preserved for further recognition by the Rev protein. In analogy with previous work by the author, it is shown that the destabilization by site-directed mutagenesis of the secondary structure for a non-chain-specific recognition site enhances the Rev response.

摘要

我们预测了在HIV-1与Rev蛋白相互作用调控中起作用的CAR(顺式抗阻遏序列)的亚稳二级结构。我们证明,env RNA中7364至7559位核苷酸之间维持的活性结构是最可能的亚稳结构,其形成受动力学控制而非热力学决定。该结构是通过蒙特卡罗模拟获得的,该模拟计算了在病毒RNA的CAR部分组装时发生的重折叠事件。因此,二级结构的调控作用在新RNA合成后立即确定,并得以保留以供Rev蛋白进一步识别。与作者之前的工作类似,结果表明,通过定点诱变破坏非链特异性识别位点的二级结构会增强Rev反应。

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