• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Structural basis of oligomerization in the stalk region of dynamin-like MxA
【24h】

Structural basis of oligomerization in the stalk region of dynamin-like MxA

机译：dynamin样MxA茎区域低聚的结构基础

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

The interferon-inducible dynamin-like myxovirus resistance protein 1 (MxA; also called MX1) GTPase is a key mediator of cell-autonomous innate immunity against pathogens such as influenza viruses. MxA partially localizes to COPI-positive membranes of the smooth endoplasmic reticulum-Golgi intermediate compartment. At the point of infection, it redistributes to sites of viral replication and promotes missorting of essential viral constituents. It has been proposed that the middle domain and the GTPase effector domain of dynamin-like GTPases constitute a stalk that mediates oligomerization and transmits conformational changes from the G domain to the target structure; however, the molecular architecture of this stalk has remained elusive. Here we report the crystal structure of the stalk of human MxA, which folds into a four-helical bundle. This structure tightly oligomerizes in the crystal in a criss-cross pattern involving three distinct interfaces and one loop. Mutations in each of these interaction sites interfere with native assembly, oligomerization, membrane binding and antiviral activity of MxA. On the basis of these results, we propose a structural model for dynamin oligomerization and stimulated GTP hydrolysis that is consistent with previous structural predictions and has functional implications for all members of the dynamin family.
机译：干扰素诱导的类似动力蛋白的粘液病毒抗性蛋白1（MxA；也称为MX1）GTPase是针对病原体（如流感病毒）的细胞自主先天免疫的关键介体。 MxA部分位于平滑内质网-高尔基体中间隔室的COPI阳性膜。在感染时，它会重新分布到病毒复制位点，并促进必需病毒成分的错误表达。有人提出，像dynamin样的GTPases的中间结构域和GTPase效应结构域构成了一个茎，该茎介导寡聚并从G结构域向靶结构传递构象变化。但是，该茎的分子结构仍然难以捉摸。在这里，我们报告了人类MxA茎的晶体结构，该结构折叠成四螺旋束。这种结构在晶体中紧密纵横交错，涉及三个不同的界面和一个环。这些相互作用位点中的每个突变都会干扰MxA的天然装配，寡聚，膜结合和抗病毒活性。在这些结果的基础上，我们提出了一种用于动力蛋白低聚和刺激的GTP水解的结构模型，该模型与先前的结构预测一致，并且对动力蛋白家族的所有成员具有功能意义。

著录项

  • 来源
    《Nature》 |2010年第7297期|p.502-506|共5页
  • 作者

    Song Gao; Alexander von der Malsburg; Susann Paeschke; Joachim Behlke; Otto Haller; Georg Kochs; Oliver Daumke;

  • 作者单位

    Max-Delbrueck-Centrum for Molecular Medicine, Crystallography, Robert-Roessle-Strasse 10,13125 Berlin, Germany Institute for Chemistry and Biochemistry, Free University Berlin, Takustrasse 3,14195 Berlin, Germany;

    Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany;

    Max-Delbrueck-Centrum for Molecular Medicine, Crystallography, Robert-Roessle-Strasse 10,13125 Berlin, Germany;

    Max-Delbrueck-Centrum for Molecular Medicine, Crystallography, Robert-Roessle-Strasse 10,13125 Berlin, Germany;

    Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany;

    Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany;

    Max-Delbrueck-Centrum for Molecular Medicine, Crystallography, Robert-Roessle-Strasse 10,13125 Berlin, Germany Institute of Medical Physics and Biophysics, Charite, Ziegelstrasse 5-9,10117 Berlin, Germany;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);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