Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Viruses. 2020 Jan 30;12(2):161. doi: 10.3390/v12020161.
Paramyxovirus (PMV) entry requires the coordinated action of two envelope glycoproteins, the receptor binding protein (RBP) and fusion protein (F). The sequence of events that occurs during the PMV entry process is tightly regulated. This regulation ensures entry will only initiate when the virion is in the vicinity of a target cell membrane. Here, we review recent structural and mechanistic studies to delineate the entry features that are shared and distinct amongst the . In general, we observe overarching distinctions between the protein-using RBPs and the sialic acid- (SA-) using RBPs, including how their stalk domains differentially trigger F. Moreover, through sequence comparisons, we identify greater structural and functional conservation amongst the PMV fusion proteins, as compared to the RBPs. When examining the relative contributions to sequence conservation of the globular head versus stalk domains of the RBP, we observe that, for the protein-using PMVs, the stalk domains exhibit higher conservation and find the opposite trend is true for SA-using PMVs. A better understanding of conserved and distinct features that govern the entry of protein-using versus SA-using PMVs will inform the rational design of broader spectrum therapeutics that impede this process.
副黏病毒 (PMV) 的进入需要两种包膜糖蛋白的协调作用，即受体结合蛋白 (RBP) 和融合蛋白 (F)。PMV 进入过程中发生的事件序列受到严格调控。这种调控确保只有当病毒颗粒接近靶细胞膜时，进入才会开始。在这里，我们回顾了最近的结构和机制研究，以描绘在 中共享和独特的进入特征。一般来说，我们观察到使用蛋白的 RBPs 和使用唾液酸 (SA) 的 RBPs 之间存在总体差异，包括它们的茎域如何差异地触发 F。此外，通过序列比较，我们发现 PMV 融合蛋白在结构和功能上比 RBPs 更保守。当检查 RBP 球状头部与茎域对序列保守性的相对贡献时，我们观察到，对于使用蛋白的 PMV 而言，茎域表现出更高的保守性，而对于使用 SA 的 PMV 则相反。更好地理解控制使用蛋白的 PMV 与使用 SA 的 PMV 进入的保守和独特特征将为设计阻碍该过程的更广泛谱治疗药物提供信息。
