...
  • 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 >Structures of p63 DNA binding domain in complexes with half-site and with spacer-containing full response elements
【24h】

Structures of p63 DNA binding domain in complexes with half-site and with spacer-containing full response elements

机译：p63 DNA结合域的结构，具有半位点和含间隔子的完整应答元件

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

Transcription factor p63, a p53 family member, plays a role in epithelial cell development, cell cycle arrest, apoptosis, and tumor-igenesis. Point mutations, primarily in the DNA binding domain (p63DBD), lead to malformation syndromes. To gain insight into differences between p63 and p53 and the impact of mutations on the structure, we have determined two crystal structures of p63DBD in complex with A/T-rich response elements. One complex contains a 10-bp DNA half-site response element (5'AAACATGT-TT3) and the other contains a 22-bp DNA full response element with a 2-bp spacer between two half-sites (5 AAACATGTTTTAAAA-CATGTTT3'). In both structures, each half-site binds a p63DBD dimer. The two p63DBD dimers do not interact in the presence of the DNA spacer, whereas they interact with one another in the p63DBD/10-bp complex where the DNA simulates a full response element by packing end-to-end. A unique dimer-dimer interaction involves a variable loop region, which differs in length and sequence from the counterpart loop of p53DBD. The DNA trajectories in both structures assume superhelical conformations. Surface plasmon resonance studies of p63DBD/DNA binding yielded K_d = 11.7 μM for a continuous full response element, whereas binding was undetectable with the 22-bp DNA, suggesting an important contribution of a p63DBD interdimer interface to binding and establishing that p63DBD affinity to the response element is approximately 1,000-fold lower than that of p53DBD. Analyses of the structural consequences of p63DBD mutations that cause developmental defects show that, although some mutations affect DNA binding directly, the majority affects protein stability.
机译：转录因子p63是p53家族成员，在上皮细胞发育，细胞周期停滞，凋亡和肿瘤发生中发挥作用。主要在DNA结合域（p63DBD）中的点突变会导致畸形综合征。为了深入了解p63和p53之间的差异以及突变对结构的影响，我们确定了富含A / T响应元件的p63DBD的两个晶体结构。一种复合物包含一个10 bp的DNA半位点应答元件（5'AAACATGT-TT3），另一种复合物包含22 bp的DNA完整应答元件，在两个半位点之间具有2 bp的间隔子（5 AAACATGTTTTAAAA-CATGTTT3'） 。在这两种结构中，每个半位均结合一个p63DBD二聚体。两个p63DBD二聚体在存在DNA间隔基的情况下不相互作用，而在p63DBD / 10-bp复合物中彼此相互作用，其中DNA通过端对端包装来模拟完整的响应元件。独特的二聚体-二聚体相互作用涉及可变的环区域，该区域的长度和序列与p53DBD的对应环不同。两种结构中的DNA轨迹都具有超螺旋构象。 p63DBD / DNA结合的表面等离振子共振研究得出连续完整响应元件的K_d = 11.7μM，而22 bp DNA无法检测到结合，表明p63DBD间二聚体界面对结合具有重要贡献，并建立了p63DBD对P63DBD的亲和力应答元件比p53DBD低约1,000倍。对导致发育缺陷的p63DBD突变的结构后果的分析表明，尽管某些突变直接影响DNA结合，但大多数影响蛋白质稳定性。

著录项

  • 来源
  • 作者

    Chen Chen; Natalia Gorlatova; Zvi Kelman; Osnat Herzberg;

  • 作者单位

    William Myron Keck Laboratory for Structural Biology, Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850;

    William Myron Keck Laboratory for Structural Biology, Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850;

    William Myron Keck Laboratory for Structural Biology, Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850,Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742;

    William Myron Keck Laboratory for Structural Biology, Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850,Department of Chemistry and Biochemistry,University of Maryland, College Park, MD 20742;

  • 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