• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >TonB-dependent ligand interactins of the Neisseria meningitidis receptor HpuAB involved in heme-iron uptake from hemoglobin and hemoglobin-haptoglobin.
【24h】

TonB-dependent ligand interactins of the Neisseria meningitidis receptor HpuAB involved in heme-iron uptake from hemoglobin and hemoglobin-haptoglobin.

机译：脑膜炎奈瑟氏球菌受体HpuAB的TonB依赖性配体相互作用素与血红蛋白和血红蛋白-触珠蛋白的血红素铁摄取有关。

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 ability to acquire the essential nutrient iron (Fe) within the human host is an important determinant of microbial pathogenesis. Neisseria meningitidis (NM) is an exclusively human pathogen that exploits multiple strategies to scavenge Fe directly from host carrier proteins. NM expresses a family of two-component Fe transporters dependent on TonB to energize Fe uptake. This study focused on HpuAB, a receptor comprised of a TonB-dependent channel protein (HpuB) and an accessory lipoprotein (HpuA). HpuAB mediates the uptake of heme-Fe from hemoglobin (Hb) and hemoglobin-haptoglobin (HbHp) complexes. This dissertation research characterized HpuAB structure, the role of receptor components, and the interactions of HpuAB with its ligands. Protease accessibility studies support a model in which a large C-terminal domain of HpuA physically interacts with HpuB to form a surface-exposed bipartite complex. The conformation of HpuAB was sensitive to the TonB-mediated energy state of the receptor. We showed that HpuAB binds to seven distinct ligands---Hb, and three structurally distinct phenotypes of apo-Hp and HbHp complexes. Growth assays and measurement of receptor-ligand binding kinetics revealed that HbHp complexes are the preferred ligand of HpuAB. HpuAB exhibited Hp phenotype specificity, binding and utilizing human-specific polymeric 2-2 HbHp more effectively than monomeric 1-1 HbHp. Analysis of isogenic Hpu mutants confirmed that both HpuA and HpuB are required for growth with Hb Fe sources. HpuB expressed alone binds with reduced capacity to Hb and with impaired affinity to all Hp and HbHp types. Despite being required for heme-Fe uptake and normal ligand interactions, no definite role for HpuA in ligand binding was observed. Finally, the energy state of HpuAB exerted a dramatic effect on the kinetics of ligand interactions. TonB and an intact proton motive force gradient were both necessary for the release of Hb and HbHp from HpuAB. This study significantly extended our understanding of the biochemical mechanisms of HpuAB-mediated Fe acquisition and characterized the dynamic, energy-dependent interactions of HpuAB with Hb and HbHp ligands.*; *This dissertation is multimedia (contains text and other applications not available in printed format).
机译：在人体宿主中获得必需营养铁的能力是微生物发病机理的重要决定因素。脑膜炎奈瑟氏球菌（NM）是人类的唯一病原体，它利用多种策略直接从宿主载体蛋白中清除铁。 NM表达依赖于TonB激发铁吸收的两组分铁转运蛋白家族。这项研究的重点是HpuAB，一种由TonB依赖性通道蛋白（HpuB）和辅助脂蛋白（HpuA）组成的受体。 HpuAB介导从血红蛋白（Hb）和血红蛋白-触珠蛋白（HbHp）复合物中摄取血红素铁。本文研究了HpuAB的结构，受体成分的作用以及HpuAB与其配体的相互作用。蛋白酶可及性研究支持一种模型，其中HpuA的大C末端结构域与HpuB物理相互作用形成表面暴露的二聚体复合物。 HpuAB的构象对受体的TonB介导的能量状态敏感。我们表明，HpuAB结合七个不同的配体--- Hb，以及载脂蛋白-Hp和HbHp复合物的三个结构上不同的表型。生长测定和受体-配体结合动力学的测量表明，HbHp复合物是HpuAB的优选配体。 HpuAB表现出Hp表型特异性，比单体1-1 HbHp更有效地结合和利用人特异性聚合2-2 HbHp。对等基因Hpu突变体的分析证实，与Hb Fe源一起生长需要HpuA和HpuB。单独表达的HpuB与Hb的结合能力降低，并且与所有Hp和HbHp类型的亲和力均受损。尽管需要血红素-铁摄取和正常的配体相互作用，但未观察到HpuA在配体结合中具有明确的作用。最后，HpuAB的能量状态对配体相互作用的动力学产生了巨大的影响。 TonB和完整的质子动力梯度对于从HpuAB中释放Hb和HbHp都是必需的。这项研究显着扩展了我们对HpuAB介导的铁获取的生化机制的了解，并表征了HpuAB与Hb和HbHp配体的动态，能量依赖性相互作用。 *本论文是多媒体的（包含文本和其他应用程序无法以打印格式显示）。

著录项

  • 作者

    Rohde, Kyle Herman.;

  • 作者单位

    The University of Oklahoma Health Sciences Center.;

  • 授予单位 The University of Oklahoma Health Sciences Center.;
  • 学科 Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2003
  • 页码 244 p.
  • 总页数 244
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 微生物学;
  • 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