• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >Four distinct structural domains in Clostridium difficile toxin B visualized using SAXS.
【24h】

Four distinct structural domains in Clostridium difficile toxin B visualized using SAXS.

机译：使用SAXS可视化艰难梭菌毒素B中的四个不同结构域。

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

Clostridium difficile is a nosocomial bacterial pathogen causing antibiotic-associated diarrhea and fatal pseudomembranous colitis. Key virulence factors are toxin A and toxin B (TcdB), two highly related toxins that are members of the large clostridial toxin family. These large multifunctional proteins disrupt cell function using a glucosyltransferase domain that is translocated into the cytosol after vesicular internalization of intact holotoxin. Although substantial information about the biochemical mechanisms of intoxication exists, research has been hampered by limited structural information, particularly of intact holotoxin. Here, we used small-angle X-ray scattering (SAXS) methods to obtain an ab initio low-resolution structure of native TcdB, which demonstrated that this molecule is monomeric in solution and possesses a highly asymmetric shape with a maximum dimension of approximately 275 A. Combining this SAXS information with crystallographic or modeled structures of individual functional domains of TcdB reveals for the first time that the three-dimensional structure of TcdB is organized into four distinct structural domains. Structures of the N-terminal glucosyltransferase, the cysteine protease, and the C-terminal repeat region can be aligned within three domains of the SAXS envelope. A fourth domain, predicted to be involved in the translocation of the glucosyltransferase, appears as a large solvent-exposed protrusion. Knowledge of the shapes and relative orientations of toxin domains provides new insight into defining functional domain boundaries and provides a framework for understanding how potential intra-domain interactions enable conformational changes to propagate between domains to facilitate intoxication processes.
机译：艰难梭菌是引起细菌性腹泻和致命性伪膜性结肠炎的医院细菌病原体。关键毒力因子是毒素A和毒素B（TcdB），这两种毒素是大梭菌毒素家族的成员中高度相关的毒素。这些大的多功能蛋白使用葡糖基转移酶结构域破坏细胞功能，该结构域在完整的全毒素囊泡内化后易位到细胞质中。尽管存在关于中毒的生物化学机制的大量信息，但有限的结构信息（尤其是完整的全毒素）限制了研究。在这里，我们使用小角度X射线散射（SAXS）方法获得了天然TcdB的从头开始的低分辨率结构，这表明该分子在溶液中为单体，并具有高度不对称的形状，最大尺寸约为275答：将此SAXS信息与TcdB各个功能域的晶体学或模型化结构相结合，首次揭示了TcdB的三维结构被组织为四个不同的结构域。 N末端葡萄糖基转移酶，半胱氨酸蛋白酶和C末端重复区域的结构可以在SAXS信封的三个域内对齐。预计第四个结构域与葡糖基转移酶的转位有关，表现为溶剂暴露的大突起。毒素域的形状和相对方向的知识为定义功能域边界提供了新的见识，并为理解潜在的域内相互作用如何使构象变化在域之间传播以促进中毒过程提供了框架。

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