Biswas Sima, Bhagat Gaurav Kumar, Guha Dipanjan, Bagchi Angshuman
Department of Biochemistry and Biophysics, University of Kalyani, Kalyani - 741235, Nadia, West Bengal, India.
Bioinformatics Infrastructure Facility Center (BIF), University of Kalyani, Kalyani, Nadia, India.
Gene. 2023 Aug 15;877:147546. doi: 10.1016/j.gene.2023.147546. Epub 2023 Jun 5.
Circular RNAs, which have covalently closed ends, are in the class of non-coding RNAs. Recent studies reveal that they are associated with various biochemical pathways. One such involvement of circular RNAs is in the onset of different types of cancers. Though the circular RNAs are known as non-coding RNAs, some of them are found to possess the capacities to code for proteins. One such circular RNA is hsa-circ-0000437 which is known to code for a short peptide referred to as CORO1C-47aa. The peptide has anti-angiogenic activity and is associated with the prevention of endometrial cancer. The peptide binds to the PAS-B domain of the Aryl hydrocarbon Receptor Nuclear Translocator (ARNT). However, till date only the amino acid sequence of the peptide is known and no structural details of the peptide are available. Therefore, in this work, our aim was to predict how the peptide would fold and what could be its possible ligand binding sites. We used computational tools to determine the structure of the peptide refined further by molecular dynamics simulations. We then performed molecular docking simulations of the peptide with its known binding partner ARNT to gain an insight into the modes of binding as the process is associated with endometrial cancer. The possible ligand binding sites along-with the natures of the possible other different ligands of the peptide were analyzed further. From this structure function analysis study, we tried to elucidate the plausible mechanism of the involvements of the peptide in the onset of endometrial cancer. This is the first report on the structural characterization of the peptide and its modes of interactions with the partner protein ARNT. This study may therefore be useful in determining the structures of new drug candidates for the treatment of endometrial cancer.
环状RNA具有共价闭合的末端，属于非编码RNA类别。最近的研究表明，它们与各种生化途径有关。环状RNA的一个此类作用是参与不同类型癌症的发生。尽管环状RNA被认为是非编码RNA，但其中一些被发现具有编码蛋白质的能力。一种这样的环状RNA是hsa-circ-0000437，已知它编码一种称为CORO1C-47aa的短肽。该肽具有抗血管生成活性，并与子宫内膜癌的预防有关。该肽与芳烃受体核转运蛋白（ARNT）的PAS-B结构域结合。然而，迄今为止，仅知道该肽的氨基酸序列，尚无该肽的结构细节。因此，在这项工作中，我们的目的是预测该肽将如何折叠以及其可能的配体结合位点是什么。我们使用计算工具确定肽的结构，并通过分子动力学模拟进一步优化。然后，我们对该肽与其已知的结合伴侣ARNT进行分子对接模拟，以深入了解结合模式，因为该过程与子宫内膜癌有关。进一步分析了可能的配体结合位点以及该肽可能的其他不同配体的性质。通过这项结构功能分析研究，我们试图阐明该肽参与子宫内膜癌发生的可能机制。这是关于该肽的结构表征及其与伴侣蛋白ARNT相互作用模式的首次报道。因此，这项研究可能有助于确定治疗子宫内膜癌的新候选药物的结构。
