...
  • 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 >Conformation of peptides bound to the transporter associated with antigen processing (TAP)
【24h】

Conformation of peptides bound to the transporter associated with antigen processing (TAP)

机译：与抗原加工（TAP）相关的转运蛋白结合的肽构象

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 ATP-binding cassette transporter associated with antigen processing (TAP) plays a key role in the adaptive immune defense against infected or malignantly transformed cells by translocating proteasomal degradation products into the lumen of the endoplas-mic reticulum for loading onto MHC class Ⅰ molecules. The broad substrate spectrum of TAP, rendering peptides from 8 to 40 residues, including even branched or modified molecules, suggests an unforeseen structural flexibility of the substrate-binding pocket Here we used EPR spectroscopy to reveal conformational details of the bound peptides. Side-chain dynamics and environmental polarity were derived from covalently attached 2,2,5,5-tetra-methylpyrrolidine-1-oxyl spin probes, whereas 2,2,6,6-tetramethyl-piperidine-1-oxyl-4-amino-4-carboxylic acid spin-labeled peptides were used to detect backbone properties. Dependent on the spin probe's position, striking differences in affinity, dynamics, and polarity were found. The side-chains' mobility was strongly restricted at the ends of the peptide, whereas the central region was flexible, suggesting a central peptide bulge. In the end, double electron electron resonance allowed the determination of intrapeptide distances in doubly labeled peptides bound to TAP. Simulations based on a rotamer library led to the conclusion that peptides bind to TAP in an extended kinked structure, analogous to those bound to MHC class Ⅰ proteins.
机译：与抗原加工（TAP）相关的ATP结合盒转运体通过将蛋白酶体降解产物转移到内质网内腔中以装载到MHCⅠ类分子上，在针对感染或恶性转化细胞的适应性免疫防御中起关键作用。 TAP具有广泛的底物光谱，可提供8至40个残基的肽，甚至包括分支或修饰的分子，这表明底物结合袋具有不可预见的结构灵活性。在这里，我们使用EPR光谱揭示了结合肽的构象细节。侧链动力学和环境极性来自共价连接的2,2,5,5-四甲基吡咯烷-1-氧基自旋探针，而2,2,6,6-四甲基哌啶-1-氧基-4-氨基-4-羧酸自旋标记的肽用于检测骨架性质。根据旋转探针的位置，发现亲和力，动力学和极性存在显着差异。侧链的流动性在肽的末端受到严格限制，而中心区域则是柔性的，表明中心肽凸出。最后，双电子电子共振可以确定与TAP结合的双标记肽的肽内距离。基于旋转异构体库的模拟得出的结论是，肽以扩展的扭结结构与TAP结合，类似于与MHCI类蛋白结合的肽。

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