• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >A Structural and Functional Analysis of the Interaction Between HHV-7 U21 and the Class I Major Histocompatibility Complex.
【24h】

A Structural and Functional Analysis of the Interaction Between HHV-7 U21 and the Class I Major Histocompatibility Complex.

机译：HHV-7 U21与I类主要组织相容性复合物之间相互作用的结构和功能分析。

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

Human herpesvirus-7 (HHV-7) is a betaherpesvirus that infects over 90% of the population by the age of 3. Although primary infection is associated with febrile illness, long-term infection with HHV-7 is asymptomatic. In co-evolving with the host immune system, herpesviruses have developed many methods of avoiding detection and clearance during a latent or persistent infection. One common strategy is to interfere with the class I MHC antigen presentation pathway in order to evade detection from cytotoxic T lymphocytes. The HHV-7 U21 protein associates with class I MHC molecules and reroutes them to lysosomes, thereby preventing cell surface expression. The mechanism by which U21 redirects class I molecules to lysosomes is unknown and remains an active area of investigation. In this study, we undergo a thorough characterization of U21’s interaction with class I MHC molecules. We find through bioinformatic analysis that U21 itself may be a structural homolog of class I MHC, and if so is the first example of a virally-encoded class I MHC homolog shown to bind directly to the class I MHC.;We also explore the substrate specificity of U21 for class I MHC and class I MHC-like proteins, finding that U21 associates with both classical and non-classical class I MHC molecules, an unusually broad target range. We test the ability of U21 to associate with class I MHC early in the class I folding pathway, finding that U21 associates with properly-folded class I molecules displaying bound peptide. In vitro analysis reveals that U21 exists in dimeric and tetrameric form in slow equilibrium exchange, with the U21 tetramer capable of binding to class I MHC. U21 associates with class I MHC in a 4:2 ratio, a novel finding for a predicted class I MHC homolog.;We further explore the role of U21’s multimerization in the cell, identifying the putative α3 domain of U21 as sufficient for association with the full-length U21 protein. Finally, we study dominant-negative mutants of U21 to begin to elucidate a model for U21’s multimerization and explore the relationship between U21’s structure and mechanism. This work advances our understanding of the versatility of the class I MHC fold, as well as provides a paradigm for multimerization of class I MHC homologs to allow efficient association with a diverse range of class I MHC proteins.
机译：人类疱疹病毒7（HHV-7）是一种β疱疹病毒，到3岁时感染了90％以上的人群。尽管原发性感染与高热疾病有关，但长期感染HHV-7无症状。在与宿主免疫系统共同进化中，疱疹病毒已开发出许多避免在潜伏或持续感染期间进行检测和清除的方法。一种常见的策略是干扰I类MHC抗原呈递途径，以逃避细胞毒性T淋巴细胞的检测。 HHV-7 U21蛋白与I类MHC分子缔合，并将其重新引导至溶酶体，从而阻止了细胞表面表达。 U21将I类分子重定向至溶酶体的机制尚不清楚，并且仍是研究的活跃领域。在这项研究中，我们对U21与I类MHC分子的相互作用进行了全面的表征。通过生物信息学分析，我们发现U21本身可能是I类MHC的结构同源物，如果是这样的话，则是病毒编码的I类MHC同源物直接与I类MHC结合的第一个例子。 U21对I类MHC和I类MHC类蛋白的特异性，发现U21与经典和非经典I类MHC分子缔合，这是一个异常广泛的靶标范围。我们测试了U21在I类折叠途径早期与I类MHC缔合的能力，发现U21与正确折叠的展示结合肽的I类分子缔合。体外分析显示，U21以缓慢的平衡交换形式以二聚体和四聚体形式存在，并且U21四聚体能够结合I类MHC。 U21以4：2的比率与I类MHC缔合，这是预测的I类MHC同源物的新发现。;我们进一步探索U21的多聚作用在细胞中的作用，确定U21的假定α3结构域足以与U21 MHC缔合。全长U21蛋白。最后，我们研究U21的显性负突变体，以开始阐明U21的多聚化模型，并探索U21的结构与机制之间的关系。这项工作提高了我们对I类MHC折叠的多功能性的理解，并为I类MHC同源物的多聚化提供了范例，从而可以与多种I类MHC蛋白有效结合。

著录项

  • 作者

    May, Nathan Alexander.;

  • 作者单位

    The Medical College of Wisconsin.;

  • 授予单位 The Medical College of Wisconsin.;
  • 学科 Biology Molecular.;Health Sciences Immunology.;Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 242 p.
  • 总页数 242
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 高分子化学（高聚物）;
  • 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