首页> 外文期刊>Nature >Transforming binding affinities from three dimensions to two with application to cadherin clustering
【24h】

Transforming binding affinities from three dimensions to two with application to cadherin clustering

机译:将结合亲和力从三个维度转换为两个维度,并将其应用于钙粘蛋白聚类

获取原文
获取原文并翻译 | 示例
           

摘要

Membrane-bound receptors often form large assemblies resulting from binding to soluble ligands, cell-surface molecules on other cells and extracellular matrix proteins~1. For example, the association of membrane proteins with proteins on different cells (trans-interactions) can drive the oligomerization of proteins on the same cell2 (cis-interactions). A central problem in understanding the molecular basis of such phenomena is that equilibrium constants are generally measured in three-dimensional solution and are thus difficult to relate to the two-dimensional environment of a membrane surface. Here we present a theoretical treatment that converts three-dimensional affinities to two dimensions, accounting directly for the structure and dynamics of the membrane-bound molecules. Using a multiscale simulation approach, we apply the theory to explain the formation of ordered, junction-like clusters by classical cadherin adhesion proteins. The approach features atomic-scale molecular dynamics simulations to determine interdomain flexibility, Monte Carlo simulations of multidomain motion and lattice simulations of junction formation3. A finding of general relevance is that changes in interdomain motion on trans-binding have a crucial role in driving the lateral, cis-, clustering of adhesion receptors.
机译:膜结合受体通常形成大的装配体,这是由于与可溶性配体,其他细胞上的细胞表面分子以及细胞外基质蛋白〜1结合而产生的。例如,膜蛋白与不同细胞上的蛋白缔合(反式相互作用)可以驱动同一细胞上蛋白的寡聚(顺式相互作用)。理解这种现象的分子基础的中心问题是,通常在三维溶液中测量平衡常数,因此很难与膜表面的二维环境相关。在这里,我们提出了一种将三维亲和力转换为二维的理论方法,直接考虑了膜结合分子的结构和动力学。使用多尺度模拟方法,我们应用该理论解释了经典钙粘着蛋白粘附蛋白形成有序的,结状簇的现象。该方法具有原子级分子动力学模拟以确定域间柔性,多域运动的蒙特卡洛模拟和结形成的晶格模拟3。普遍相关的发现是,反式结合上域间运动的变化在驱动粘附受体的横向,顺式,成簇方面起着至关重要的作用。

著录项

  • 来源
    《Nature》 |2011年第7357期|p.510-513|共4页
  • 作者单位

    Department of Biochemistry and Molecular Biophysics, Columbia University, New York. New York 10032, USA,Howard Hughes Medical Instrtate.Voldmbion University . New York, New York 10032, USA,Center for Computational Biology and Bioinformatics. Columbia University, New York, New York, 10032. USA;

    Department of Biochemistry and Molecular Biophysics, Columbia University, New York. New York 10032, USA,Howard Hughes Medical Instrtate.Voldmbion University . New York, New York 10032, USA,Center for Computational Biology and Bioinformatics. Columbia University, New York, New York, 10032. USA;

    Department of Biochemistry and Molecular Biophysics, Columbia University, New York. New York 10032, USA,Edward S. Hirkness Eyedusttute. Columbia University, NewYork, New York 10032, USA;

    Institute of Chemistry and the Fritz Haber Research Center, The Hebrew University, Jerusalem 91904, Israel;

    Department of Biochemistry and Molecular Biophysics, Columbia University, New York. New York 10032, USA,Howard Hughes Medical Instrtate.Voldmbion University . New York, New York 10032, USA,Center for Computational Biology and Bioinformatics. Columbia University, New York, New York, 10032. 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