Computational Modeling of IN-CTD/TAR Complex to Elucidate Additional Strategies to Inhibit HIV-1 Replication.
Computational Modeling of IN-CTD/TAR Complex to Elucidate Additional Strategies to Inhibit HIV-1 Replication.
复制标题
IN-CTD/TAR 复合物的计算模型阐明了抑制 HIV-1 复制的其他策略。
DOI：
10.1007/978-1-0716-2895-9_7
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Zou,Xiaoqin
中科院分区：
文献类型：
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作者：
Qiu,Liming;Bhutoria,Savita;Kalpana,GanjamV;Zou,Xiaoqin
HIV-1整合酶（IN）是介导逆转录病毒DNA插入宿主染色体的关键酶。IN还表现出未完全阐明的其他功能，包括其结合病毒基因组RNA的能力。IN与病毒粒子内RNA结合的缺乏已被证明与形态缺陷病毒颗粒的产生相关。然而，与RNA结合的HIV-1 IN的确切结构尚不清楚。基于IN的C-末端结构域（CTD）与TAR RNA区域结合的研究以及TAR与IN-CTD结合的宿主因子INI 1相同的观察，我们计算模拟了IN-CTD/TAR复合物的结构。当实验方法无法解决复杂结构时，核酸与蛋白质结合的计算建模是理解大分子相互作用的一种有价值的方法。IN-CTD/TAR复合物的当前模型可能有助于进一步理解这种相互作用，并可能导致IN-CTD/RNA相互作用的治疗靶向，以抑制HIV-1复制。
HIV-1 integrase (IN) is a key enzyme that is essential for mediating the insertion of retroviral DNA into the host chromosome. IN also exhibits additional functions which are not fully elucidated, including its ability to bind to viral genomic RNA. Lack of binding of IN to RNA within the virions has been shown to be associated with production of morphologically defective virus particles. However, the exact structure of HIV-1 IN bound to RNA is not known. Based on the studies that C-terminal domain (CTD) of IN binds to TAR RNA region and based on the observation that TAR and the host factor INI1 binding to IN-CTD are identical, we computationally modelled the IN-CTD/TAR complex structure. Computational modeling of nucleic acid binding to proteins is a valuable method to understand the macromolecular interaction when experimental methods of solving the complex structures are not feasible. The current model of the IN-CTD/TAR complex may facilitate further understanding of this interaction and may lead to therapeutic targeting of IN-CTD/RNA interactions to inhibit HIV-1 replication.