• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >The spatial architecture of protein function and adaptation
【24h】

The spatial architecture of protein function and adaptation

机译：蛋白质功能和适应性的空间结构

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

Statistical analysis of protein evolution suggests a design for natural proteins in which sparse networks of coevolving amino acids (termed sectors) comprise the essence of three-dimensional structure and function. However, proteins are also subject to pressures deriving from the dynamics of the evolutionary process itself-the ability to tolerate mutation and to be adaptive to changing selection pressures. To understand the relationship of the sector architecture to these properties, we developed a high-throughput quantitative method for a comprehensive single-mutation study in which every position is substituted individually to every other amino acid. Using a PDZ domain (PSD95~(pdz3)) model system, we show that sector positions are functionally sensitive to mutation, whereas non-sector positions are more tolerant to substitution. In addition, we find that adaptation to a new binding specificity initiates exclusively through variation within sector residues. A combination of just two sector mutations located near and away from the ligand-binding site suffices to switch the binding specificity of PSD95~(pdz3) quantitatively towards a class-switching ligand. The localization of functional constraint and adaptive variation within the sector has important implications for understanding and engineering proteins.
机译：蛋白质进化的统计分析提出了一种天然蛋白质的设计，其中稀疏的共同进化氨基酸网络（称为扇区）包含三维结构和功能的本质。然而，蛋白质也要承受来自进化过程本身动力学的压力，即承受突变和适应变化的选择压力的能力。为了了解部门架构与这些属性的关系，我们开发了一种高通量定量方法用于全面的单突变研究，其中每个位置分别被其他氨基酸取代。使用PDZ域（PSD95〜（pdz3））模型系统，我们显示了扇区位置对突变功能敏感，而非扇区位置更能耐受替换。另外，我们发现对新结合特异性的适应性仅通过区段残基内的变化而开始。仅位于和远离配体结合位点的两个扇形突变的组合就足以将PSD95〜（pdz3）的结合特异性定量地切换至类别切换配体。该部门内功能约束和适应性变化的本地化对于理解和工程化蛋白质具有重要意义。

著录项

  • 来源
    《Nature》 |2012年第7422期|p.138-142|共5页
  • 作者

    Richard N. McLaughlin Jr.; Frank J. Poelwijk; Arjun Raman; Walraj S. Gosal; Rama Ranganathan;

  • 作者单位

    Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA,Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA,Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109-1024, USA;

    Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA,Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA;

    Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA,Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA;

    Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA,Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA;

    Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA,Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);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