美国德克萨斯大学奥斯汀分校Jason S. McLellan研究组解析了呼吸合胞病毒聚合酶复合体的结构。 2019年9月5日，《细胞》在线发表了这一成果。

研究人员解析了四聚体P结合RSV-L的3.2-Å的冷冻电镜结构。该结构显示了P特殊的排列，即四种单体中的每一种都采用了独特的构象。该结构合理解释了抑制剂逃逸突变体以及在减毒活疫苗候选物中观察到的突变。这些结果提供了用于确定RSV复制和转录分子基础的框架，并且有助于设计有效的RSV抑制剂。

研究人员介绍，许多针对呼吸道合胞病毒（RSV）感染的药物都在临床开发阶段，包括靶向病毒转录和复制的小分子。RSV感染过程由包含RNA依赖性RNA聚合酶（L）和四聚体磷蛋白（P）的复合物催化。除了其寡聚化结构域外， RSV P将多种蛋白质募集到聚合酶复合物中，这被认为是固有的、无序的。尽管L和P的结构在RSV转录和复制中起关键作用，但它们的结构仍然未被解析。

附：英文原文

Title: Structure of the Respiratory Syncytial Virus Polymerase Complex

Author: Morgan S.A. Gilman, Cheng Liu, Amy Fung, Ishani Behera, Paul Jordan, Peter Rigaux, Nina Ysebaert, Sergey Tcherniuk, Julien Sourimant, Jean-Franois Eléout, Priscila Sutto-Ortiz, Etienne Decroly, Dirk Roymans, Zhinan Jin, Jason S. McLellan

Issue&Volume: 5 September 2019

Abstract: Numerous interventions are in clinical development for respiratory syncytial virus (RSV) infection, including small molecules that target viral transcription and replication. These processes are catalyzed by a complex comprising the RNA-dependent RNA polymerase (L) and the tetrameric phosphoprotein (P). RSV P recruits multiple proteins to the polymerase complex and, with the exception of its oligomerization domain, is thought to be intrinsically disordered. Despite their critical roles in RSV transcription and replication, structures of L and P have remained elusive. Here, we describe the 3.2- cryo-EM structure of RSV L bound to tetrameric P. The structure reveals a striking tentacular arrangement of P, with each of the four monomers adopting a distinct conformation. The structure also rationalizes inhibitor escape mutants and mutations observed in live-attenuated vaccine candidates. These results provide a framework for determining the molecular underpinnings of RSV replication and transcription and should facilitate the design of effective RSV inhibitors.

DOI: 10.1016/j.cell.2019.08.014

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30902-X