• 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 >ARNT PAS-B has a fragile native state structure with an alternative β-sheet register nearby in sequence space
【24h】

ARNT PAS-B has a fragile native state structure with an alternative β-sheet register nearby in sequence space

机译：ARNT PAS-B具有脆弱的原始状态结构，序列空间附近有一个备用β-sheet寄存器

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 aryl hydrocarbon receptor nuclear translocator (ARNT) is a basic helix-loop-helix Period/ARNT/Single-minded (bHLH-PAS) protein that controls various biological pathways as part of dimeric transcrip-ttonal regulator complexes with other bHLH-PAS proteins. The two PAS domains within ARNT, PAS-A and PAS-B, are essential for the formation of these complexes because they mediate protein-protein interactions via residues located on their /3-sheet surfaces. While investigating the importance of residues in ARNT PAS-B involved in these interactions, we uncovered a point mutation (Y456T) on the solvent-exposed β-sheet surface that allowed this domain to inter-convert with a second, stable conformation. Although both conformations are present in equivalent quantities in the Y456T mutant, this can be shifted almost completely to either end point by additional mutations. A high-resolution solution structure of a mutant ARNT PAS-B domain stabilized in the new conformation revealed a 3-resi-due slip in register and accompanying inversion of the central 1β-strand. We have demonstrated that the new conformation has > 100-fold lower in vitro affinity for its heterodimerization partner, hypoxia-inducible factor 2a PAS-B. We speculate that the pliability in β-strand register is related to the flexibility required of ARNT to bind to several partners and, more broadly, to the abilities of some PAS domains to regulate their activities in response to small-molecule cofactors.
机译：芳基烃受体核转运子（ARNT）是基本的螺旋-环-螺旋周期/ ARNT /单心（bHLH-PAS）蛋白，可控制多种生物学途径，作为与其他bHLH-PAS蛋白的二聚转录-音调调节剂复合物的一部分。 ARNT中的两个PAS域，PAS-A和PAS-B，对于这些复合物的形成至关重要，因为它们通过位于其3页表面的残基介导蛋白质-蛋白质相互作用。在调查参与这些相互作用的ARNT PAS-B中残基的重要性时，我们在溶剂暴露的β-折叠表面上发现了一个点突变（Y456T），该点突变使该结构域与第二个稳定构象相互转化。尽管两种构象在Y456T突变体中的存在量相同，但可以通过其他突变将其几乎完全转移到任一端点。稳定在新构象中的突变体ARNT PAS-B结构域的高分辨率溶液结构揭示了3残基在套准中的滑动，并伴随着中央1β链的倒置。我们已经证明，新构象对其异源二聚体伴侣，低氧诱导因子2a PAS-B的体外亲和力低> 100倍。我们推测β-链寄存器的柔韧性与ARNT结合多个伴侣所需的灵活性有关，更广泛地说，与某些PAS结构域调节其对小分子辅因子的活性的能力有关。

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