Computational Insights on the Assembly of the Dengue Virus Membrane-Capsid-RNA Complex.

IF 2.3 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Membrane Biology Pub Date : 2025-01-19 DOI:10.1007/s00232-025-00337-4

Dwaipayan Chaudhuri, Satyabrata Majumder, Joyeeta Datta, Kalyan Giri

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Abstract

Dengue virus, an arbovirus from the genus Flavivirus in the family Flaviviridae, forms a nucleocapsid structure through interactions between its genome and multiple copies of the capsid protein. Experimental studies have confirmed the interaction between the viral capsid protein and lipid droplets, indicating a protein-lipid interaction. Cryo-EM studies show that in immature viruses, the nucleocapsid is located close to the viral membrane. This study uses multiple MD simulations to explore the orientation of the capsid protein relative to the lipid membrane, focusing on how the protein's hydrophobic pocket interacts with the membrane. We also investigated the interaction between the capsid protein and RNA, considering the effects of sequence length and identity. Finally, we construct a model of the lipid-protein-RNA complex, demonstrating that the capsid protein's hydrophobic pocket interacts with the membrane, while the positively charged H4 helix interacts with the negatively charged RNA. This research may identify crucial interactions for immature virus particle formation and provide insights for future therapeutic interventions.

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登革病毒膜-衣壳- rna复合物组装的计算见解。

登革热病毒是一种来自黄病毒科黄病毒属的虫媒病毒，通过其基因组与衣壳蛋白的多个拷贝之间的相互作用形成核衣壳结构。实验研究证实了病毒衣壳蛋白与脂滴之间的相互作用，表明存在蛋白-脂相互作用。低温电镜研究表明，在未成熟的病毒中，核衣壳位于病毒膜附近。本研究使用多个MD模拟来探索衣壳蛋白相对于脂质膜的取向，重点研究蛋白质的疏水口袋如何与膜相互作用。考虑到序列长度和同源性的影响，我们还研究了衣壳蛋白和RNA之间的相互作用。最后，我们构建了脂质-蛋白-RNA复合物的模型，证明衣壳蛋白的疏水性口袋与膜相互作用，而带正电的H4螺旋与带负电的RNA相互作用。这项研究可能会确定未成熟病毒颗粒形成的关键相互作用，并为未来的治疗干预提供见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Membrane Biology 生物-生化与分子生物学

CiteScore

4.80

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The Journal of Membrane Biology is dedicated to publishing high-quality science related to membrane biology, biochemistry and biophysics. In particular, we welcome work that uses modern experimental or computational methods including but not limited to those with microscopy, diffraction, NMR, computer simulations, or biochemistry aimed at membrane associated or membrane embedded proteins or model membrane systems. These methods might be applied to study topics like membrane protein structure and function, membrane mediated or controlled signaling mechanisms, cell-cell communication via gap junctions, the behavior of proteins and lipids based on monolayer or bilayer systems, or genetic and regulatory mechanisms controlling membrane function. Research articles, short communications and reviews are all welcome. We also encourage authors to consider publishing ''negative'' results where experiments or simulations were well performed, but resulted in unusual or unexpected outcomes without obvious explanations. While we welcome connections to clinical studies, submissions that are primarily clinical in nature or that fail to make connections to the basic science issues of membrane structure, chemistry and function, are not appropriate for the journal. In a similar way, studies that are primarily descriptive and narratives of assays in a clinical or population study are best published in other journals. If you are not certain, it is entirely appropriate to write to us to inquire if your study is a good fit for the journal.