Sun Jixue, Li Yang, Liu Pi, Lin Jianping
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 West 7th Avenue, Tianjin Airport Economic Area, Tianjin 300308, People's Republic of China.
J Mol Graph Model. 2017 Jun;74:203-214. doi: 10.1016/j.jmgm.2017.04.009. Epub 2017 Apr 13.
The Zika virus has drawn worldwide attention because of the epidemic diseases it causes. It is a flavivirus that has an icosahedral protein shell constituted by an envelope glycoprotein (E-protein) and membrane protein (M-protein) in the mature virion. The multistep process of membrane fusion to infect the host cell is pH-induced. To understand the mechanism of the conformational changes in the (E-M) protein homodimer embedded in the membrane, two 200-ns accelerated dynamic simulations were performed under different pH conditions. The low pH condition weakens the interactions and correlations in both E-protein monomers and in the E-M heterodimer. The highly conserved residues, His249, His288, His323 and His446, are protonated under low pH conditions and play key roles in driving the fusion process. The analysis and discussion in this study may provide some insight into the molecular mechanism of Zika virus infection.
寨卡病毒因其引发的流行病而受到全球关注。它是一种黄病毒，在成熟病毒粒子中具有由包膜糖蛋白（E蛋白）和膜蛋白（M蛋白）构成的二十面体蛋白质外壳。膜融合感染宿主细胞的多步骤过程是由pH诱导的。为了解嵌入膜中的（E-M）蛋白同型二聚体构象变化的机制，在不同pH条件下进行了两次200纳秒的加速动力学模拟。低pH条件削弱了E蛋白单体以及E-M异源二聚体中的相互作用和相关性。高度保守的残基His249、His288、His323和His446在低pH条件下被质子化，并在驱动融合过程中起关键作用。本研究中的分析和讨论可能为寨卡病毒感染的分子机制提供一些见解。
