Chaudhuri Dwaipayan, Majumder Satyabrata, Datta Joyeeta, Giri Kalyan
Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, 700073, India.
J Membr Biol. 2025 Feb;258(1):75-96. doi: 10.1007/s00232-025-00337-4. Epub 2025 Jan 19.
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.
登革病毒是黄病毒科黄病毒属的一种虫媒病毒，通过其基因组与衣壳蛋白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，表明存在蛋白质 - 脂质相互作用。冷冻电镜研究表明，在未成熟病毒中，核衣壳位于靠近病毒膜的位置。本研究使用多个分子动力学模拟来探索衣壳蛋白相对于脂质膜的取向，重点关注蛋白质的疏水口袋如何与膜相互作用。我们还研究了衣壳蛋白与RNA之间的相互作用，考虑了序列长度和同一性的影响。最后，我们构建了脂质 - 蛋白质 - RNA复合物模型，证明衣壳蛋白的疏水口袋与膜相互作用，而带正电荷的H4螺旋与带负电荷的RNA相互作用。这项研究可能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。
