Li Long, Lok Shee-Mei, Yu I-Mei, Zhang Ying, Kuhn Richard J, Chen Jue, Rossmann Michael G
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Science. 2008 Mar 28;319(5871):1830-4. doi: 10.1126/science.1153263.
Many viruses go through a maturation step in the final stages of assembly before being transmitted to another host. The maturation process of flaviviruses is directed by the proteolytic cleavage of the precursor membrane protein (prM), turning inert virus into infectious particles. We have determined the 2.2 angstrom resolution crystal structure of a recombinant protein in which the dengue virus prM is linked to the envelope glycoprotein E. The structure represents the prM-E heterodimer and fits well into the cryo-electron microscopy density of immature virus at neutral pH. The pr peptide beta-barrel structure covers the fusion loop in E, preventing fusion with host cell membranes. The structure provides a basis for identifying the stages of its pH-directed conformational metamorphosis during maturation, ending with release of pr when budding from the host.
许多病毒在组装的最后阶段会经历一个成熟步骤，然后才会传播到另一个宿主。黄病毒的成熟过程由前体膜蛋白（prM）的蛋白水解切割所引导，将无活性的病毒转化为感染性颗粒。我们已经确定了一种重组蛋白的2.2埃分辨率晶体结构，其中登革病毒prM与包膜糖蛋白E相连。该结构代表了prM-E异二聚体，并且很好地拟合了中性pH下未成熟病毒的冷冻电子显微镜密度。pr肽β桶结构覆盖了E中的融合环，防止与宿主细胞膜融合。该结构为识别其在成熟过程中pH引导的构象变形阶段提供了基础，该过程在从宿主出芽时以pr的释放结束。
