• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >Extensive mutagenesis of the HSV-1 gB ectodomain reveals remarkable stability of its postfusion form
【24h】

Extensive mutagenesis of the HSV-1 gB ectodomain reveals remarkable stability of its postfusion form

机译：HSV-1 gB胞外域的广泛诱变显示其融合后形式的显着稳定性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Viral fusogens mediate the merger of the viral envelope and cellular membrane during viral entry. These proteins share little sequence similarity but all are thought to act by refolding through a series of conformational intermediates from the metastable prefusion form to the stable postfusion form. Crystal structures of both prefusion and postfusion forms have illuminated the conformational pathways of several viral fusogens. By contrast, only the structure of the postfusion form is available for glycoprotein B (gB), the conserved fusogen of herpesviruses. To gain insight into the nature of the fusogenic conformational changes in gB, we used several approaches aimed at engineering the prefusion form of the herpes simplex virus type 1 gB ectodomain, including modifications intended to stabilize the prefusion form and novel mutations aimed at destabilizing the postfusion form. We found that the postfusion conformation of gB is remarkably stable and resistant to perturbations. Several mutations successfully destabilized the gB trimer, identifying regions that are critical for the stability of the postfusion form. Yet, none of the constructs adopted the prefusion conformation. We propose that the soluble ectodomain of gB folds into the postfusion form without first adopting the prefusion intermediate. These results suggest that other regions of gB, including the transmembrane region and the cytoplasmic domain, may be necessary to establish and maintain the metastable prefusion conformation.
机译：病毒融合剂在病毒进入过程中介导病毒被膜和细胞膜的融合。这些蛋白质几乎没有序列相似性，但是全部被认为是通过一系列构象中间体从亚稳态预融合形式重折叠为稳定的后融合形式起作用的。融合前和融合后形式的晶体结构都阐明了几种病毒性融合剂的构象途径。相比之下，只有融合后形式的结构可用于糖蛋白B（gB），这是疱疹病毒的保守融合蛋白。为了深入了解gB融合构象变化的性质，我们使用了几种旨在工程化1型单纯疱疹病毒gB胞外域的融合形式的方法，包括旨在稳定融合形式的修饰和旨在破坏融合后稳定性的新突变。形成。我们发现，gB的融合后构象非常稳定且抗扰动。几个突变成功地使gB三聚体不稳定，从而确定了对融合后形式的稳定性至关重要的区域。然而，没有一种构建体采用预融合构象。我们建议不首先采用融合前中间体，将gB的可溶性胞外域折叠成融合后形式。这些结果表明，gB的其他区域，包括跨膜区域和胞质域，可能是建立和维持亚稳态预融合构象所必需的。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号