Laboratoire de Cristallographie et RMN biologiques, Université Paris-Descartes, CNRS UMR 8015, 4 avenue de l'Observatoire, 75006 Paris, France.
Virus Res. 2012 Nov;169(2):324-39. doi: 10.1016/j.virusres.2012.06.006. Epub 2012 Jun 18.
HIV-1 reverse transcription is initiated from a tRNA(Lys)(3) molecule annealed to the viral RNA at the primer binding site (PBS). The annealing of tRNA(Lys)(3) requires the opening of its three-dimensional structure and RNA rearrangements to form an efficient initiation complex recognized by the reverse transcriptase. This annealing is mediated by the nucleocapsid protein (NC). In this paper, we first review the actual knowledge about HIV-1 viral RNA and tRNA(Lys)(3) structures. Then, we summarize the studies explaining how NC chaperones the formation of the tRNA(Lys)(3)/PBS binary complex. Additional NMR data that investigated the NC interaction with tRNA(Lys)(3) D-loop are presented. Lastly, we focused on the additional interactions occurring between tRNA(Lys)(3) and the viral RNA and showed that they are dependent on HIV-1 isolates, i.e. the sequence and the structure of the viral RNA.
HIV-1 逆转录是从与病毒 RNA 在引物结合位点 (PBS) 处退火的 tRNA(Lys)(3)分子开始的。tRNA(Lys)(3)的退火需要其三维结构的打开和 RNA 重排,以形成被逆转录酶识别的有效起始复合物。这种退火是由核衣壳蛋白 (NC) 介导的。在本文中,我们首先回顾了关于 HIV-1 病毒 RNA 和 tRNA(Lys)(3)结构的现有知识。然后,我们总结了解释 NC 如何协助形成 tRNA(Lys)(3)/PBS 二元复合物的研究。还介绍了研究 NC 与 tRNA(Lys)(3)D 环相互作用的额外 NMR 数据。最后,我们重点研究了 tRNA(Lys)(3)与病毒 RNA 之间发生的其他相互作用,并表明它们依赖于 HIV-1 分离株,即病毒 RNA 的序列和结构。