Structure of the immature dengue virus at low pH primes proteolytic maturation
Structure of the immature dengue virus at low pH primes proteolytic maturation
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DOI：
10.1126/science.1153264
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发表时间：
2008-03-28
期刊：
影响因子：
56.9
通讯作者：
Chen, Jue
中科院分区：
文献类型：
--
作者：
Yu, I-Mei;Zhang, Wei;Chen, Jue
未成熟黄病毒的胞内切割是产生E糖蛋白膜融合潜力的组装过程中的关键步骤。利用冷冻电子显微镜，我们发现未成熟的登革热颗粒在低pH值下经历了可逆的构象变化，使它们容易被Furin切割。在pH为6.0时，E蛋白以人字形排列，Pr多肽对接在融合环上，类似于成熟病毒粒子的构型。在裂解后，Pr的解离依赖于pH，这表明在跨高尔基网络的酸性环境中，Pr被保留在病毒粒子上，以阻止膜融合。这些结果提示了黄病毒在宿主细胞分泌途径中被处理和稳定的机制。
Intracellular cleavage of immature flaviviruses is a critical step in assembly that generates the membrane fusion potential of the E glycoprotein. With cryo- electron microscopy we show that the immature dengue particles undergo a reversible conformational change at low pH that renders them accessible to furin cleavage. At a pH of 6.0, the E proteins are arranged in a herringbone pattern with the pr peptides docked onto the fusion loops, a configuration similar to that of the mature virion. After cleavage, the dissociation of pr is pH- dependent, suggesting that in the acidic environment of the trans- Golgi network pr is retained on the virion to prevent membrane fusion. These results suggest a mechanism by which flaviviruses are processed and stabilized in the host cell secretory pathway.