Nguyen Tam Luong, Schoehn Guy, Weissenhorn Winfried, Hermone Ann R, Burnett James C, Panchal Rekha G, McGrath Connor, Zaharevitz Dan W, Aman M Javad, Gussio Rick, Bavari Sina
Target Structure-Based Drug Discovery Group, Developmental Therapeutics Program, SAIC, National Cancer Institute, Frederick, MD 21702, USA.
J Struct Biol. 2005 Jul;151(1):30-40. doi: 10.1016/j.jsb.2005.02.013.
The matrix protein VP40 is an indispensable component of viral assembly and budding by the Ebola virus. VP40 is a monomer in solution, but can fold into hexameric and octameric states, two oligomeric conformations that play central roles in the Ebola viral life cycle. While the X-ray structures of monomeric and octameric VP40 have been determined, the structure of hexameric VP40 has only been solved by three-dimensional electron microscopy (EM) to a resolution of approximately 30 A. In this paper, we present the refinement of the EM reconstruction of truncated hexameric VP40 to approximately 20 A and the construction of an all-atom model (residues 44-212) using the EM model at approximately 20 A and the X-ray structure of monomeric VP40 as templates. The hexamer model suggests that the monomer-hexamer transition involves a conformational change in the N-terminal domain that is not evident during octamerization and therefore, may provide the basis for elucidating the biological function of VP40.
基质蛋白VP40是埃博拉病毒进行病毒组装和出芽所必需的成分。VP40在溶液中是单体，但可折叠成六聚体和八聚体状态，这两种寡聚构象在埃博拉病毒生命周期中起核心作用。虽然已确定单体和八聚体VP40的X射线结构，但六聚体VP40的结构仅通过三维电子显微镜（EM）解析到约30埃的分辨率。在本文中，我们展示了将截短的六聚体VP40的EM重建细化至约20埃，并以约20埃的EM模型和单体VP40的X射线结构为模板构建全原子模型（44 - 212位氨基酸残基）。六聚体模型表明，单体 - 六聚体转变涉及N端结构域的构象变化，这种变化在八聚化过程中不明显，因此可能为阐明VP40的生物学功能提供基础。
