...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Capture and imaging of a prehairpin fusion intermediate of the paramyxovirus PIV5
【24h】

Capture and imaging of a prehairpin fusion intermediate of the paramyxovirus PIV5

机译：副粘病毒PIV5的prehairpin融合中间体的捕获和成像

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

During cell entry, enveloped viruses fuse their viral membrane with a cellular membrane in a process driven by energetically favorable, large-scale conformational rearrangements of their fusion proteins. Structures of the pre- and postfusion states of the fusion proteins including paramyxovirus PIV5 F and influenza virus hemagglutinin suggest that this occurs via two intermediates. Following formation of an initial complex, the proteins structurally elongate, driving a hydrophobic N-terminal "fusion peptide" away from the protein surface into the target membrane. Paradoxically, this first conformation change moves the viral and cellular bilayers further apart. Next, the fusion proteins form a hairpin that drives the two membranes into close opposition. While the pre- and post-fusion hairpin forms have been characterized crystallographically, the transiently extended prehairpin intermediate has not been visualized. To provide evidence for this extended intermediate we measured the interbilayer spacing of a paramyxovirus trapped in the process of fusing with solid-supported bilayers. A gold-labeled peptide that binds the prehairpin intermediate was used to stabilize and specifically image F-proteins in the prehairpin intermediate. The interbilayer spacing is precisely that predicted from a computational model of the prehairpin, providing strong evidence for its structure and functional role. Moreover, the F-proteins in the prehairpin conformation preferentially localize to a patch between the target and viral membranes, consistent with the fact that the formation of the prehairpin is triggered by local contacts between F- and neighboring viral receptor-binding proteins (HN) only when HN binds lipids in its target membrane.
机译：在细胞进入过程中，被包膜的病毒在其融合蛋白的能量有利的，大规模构象重排驱动的过程中将其病毒膜与细胞膜融合。包括副粘病毒PIV5 F和流感病毒血凝素在内的融合蛋白融合前和融合后状态的结构表明，这是通过两种中间体发生的。形成初始复合物后，蛋白质在结构上伸长，从而驱动疏水性N端“融合肽”从蛋白质表面进入目标膜。矛盾的是，这种第一个构象变化使病毒和细胞双层进一步分开。接下来，融合蛋白形成发夹，使两个膜紧密相对。虽然融合前和融合后发夹的形式已经在晶体学上进行了表征，但瞬时延伸的发夹前中间体尚未显现出来。为了提供这种扩展的中间体的证据，我们测量了在与固相支持的双层融合过程中捕获的副粘病毒的双层间距。结合前发夹中间体的金标记肽用于稳定前发夹中间体中的F蛋白并使之成像。双层间的间隔正是从前发夹的计算模型预测的，为它的结构和功能作用提供了有力的证据。此外，前发夹构型中的F蛋白优先定位在靶标和病毒膜之间的斑块上，这与前发夹的形成是由F-与邻近病毒受体结合蛋白（HN）之间的局部接触触发的事实相一致的。仅当HN结合其靶膜中的脂质时。

著录项

  • 来源
  • 作者

    Yong Ho Kim; Jason E. Donald; Gevorg Grigoryan; George P. Leser; Alexander Y. Fadeev; Robert A. Lamb; William F. DeGrado;

  • 作者单位

    Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104;

    Department of Biochemistry and Biophysics, University of Pennsylvania,Philadelphia, PA 19104;

    Department of Biochemistry and Biophysics, University of Pennsylvania,Philadelphia, PA 19104,Department of Computer Science, Dartmouth College, Hanover, NH 03755;

    Howard Hughes Medical Institute and Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201;

    Department of Chemistry and Biochemistry, Seton Hall University, South Orange, NJ 07079;

    Howard Hughes Medical Institute and Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201;

    Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104,Department of Biochemistry and Biophysics, University of Pennsylvania,Philadelphia, PA 19104,Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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