...
  • 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 >Cation-π interaction regulates ligand-binding affinity and signaling of integrin α_4β_7
【24h】

Cation-π interaction regulates ligand-binding affinity and signaling of integrin α_4β_7

机译：阳离子-π相互作用调节配体结合亲和力和整联蛋白α_4β_7的信号传导

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

Integrin α4β7 mediates rolling and firm adhesion of leucocytes, two of the critical steps in leukocyte migration and tissue specific homing. Affinity of α4β7 for ligand is dynamically regulated by three interlinked metal ion-binding sites in β7-subunit I domain. In this study, we found that Phe185 (F185), a highly conserved aromatic residue in β7-subunit, links the specificity-determining loop and the synergistic metal ion-binding site (SyMBS) through cation-π interaction. Mutations of F185 that disrupted the SyMBS cation-F185 interaction led to deficient firm cell adhesion mediated by high affinity α4β7, and only slightly affected rolling adhesion mediated by low affinity α4β7. Disruption of SyMBS cation-F185 interaction induced partial extension of integrin ectodomain and separation of cytoplasmic tails, and impaired α4β7-mediated bidirectional signaling. In addition, loss of SyMBS cation-F185 interaction increased paxillin expression and promoted paxillin-integrin binding, leading to deficient cell spreading. Furthermore, integrin α4β7-mediated cell migration was decreased by the abolishment of SyMBS cation-F185 interaction. Thus, these findings reveal a cation-π interaction playing vital roles in the regulation of integrin affinity, signaling, and biological functions.
机译：整联蛋白α4β7介导白细胞的滚动和牢固粘附，这是白细胞迁移和组织特异性归巢的两个关键步骤。 α4β7对配体的亲和力由β7亚基I结构域中的三个相互连接的金属离子结合位点动态调节。在这项研究中，我们发现Phe185（F185）是β7亚基中高度保守的芳香族残基，通过阳离子-π相互作用将特异性确定环与协同金属离子结合位点（SyMBS）连接起来。破坏SyMBS阳离子与F185相互作用的F185突变导致由高亲和力α4β7介导的牢固的细胞粘附不足，而对由低亲和力α4β7介导的滚动粘附的影响很小。 SyMBS阳离子-F185相互作用的破坏引起整联蛋白胞外域的部分延伸和细胞质尾巴的分离，并削弱了α4β7介导的双向信号传导。此外，SyMBS阳离子-F185相互作用的丧失增加了Paxillin的表达并促进了Paxillin-整合素的结合，从而导致细胞扩散不足。此外，整合素α4β7介导的细胞迁移通过取消SyMBS阳离子-F185相互作用而减少。因此，这些发现揭示了阳离子-π相互作用在整联蛋白亲和力，信号传导和生物学功能的调节中起着至关重要的作用。

著录项

  • 来源
  • 作者

    YouDong Pan; Kun Zhang; JunPeng Qi; Jiao Yue; Timothy A. Springer; and JianFeng Chen;

  • 作者单位

    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Shanghai 200031, China;

    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Shanghai 200031, China;

    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Shanghai 200031, China;

    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Shanghai 200031, China;

    The Immune Disease Institute, Children's Hospital Boston, and Department of Pathology, Harvard Medical School,3 Blackfan Circle, Boston, MA 02115;

    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Shanghai 200031, China;

  • 收录信息 美国《科学引文索引》(SCI);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