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Direct visualization reveals dynamics of a transient intermediate during protein assembly

机译:直接可视化显示蛋白质组装过程中瞬态中间体的动力学

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摘要

Interactions between proteins underlie numerous biological functions. Theoretical work suggests that protein interactions initiate with formation of transient intermediates that subsequently relax to specific, stable complexes. However, the nature and roles of these transient intermediates have remained elusive. Here, we characterized the global structure, dynamics, and stability of a transient, on-pathway intermediate during complex assembly between the Signal Recognition Particle (SRP) and its receptor. We show that this intermediate has overlapping but distinct interaction interfaces from that of the final complex, and it is stabilized by long-range electrostatic interactions. A wide distribution of conformations is explored by the intermediate; this distribution becomes more restricted in the final complex and is further regulated by the cargo of SRP. These results suggest a funnel-shaped energy landscape for protein interactions, and they provide a framework for understanding the role of transient intermediates in protein assembly and biological regulation.
机译:蛋白质之间的相互作用是众多生物学功能的基础。理论研究表明,蛋白质相互作用始于过渡中间体的形成,随后过渡为特定的稳定复合物。但是,这些瞬时中间体的性质和作用仍然难以捉摸。在这里,我们表征了信号识别粒子(SRP)及其受体之间复杂组装过程中瞬态,途中中间体的整体结构,动力学和稳定性。我们表明,该中间体与最终配合物具有重叠但截然不同的相互作用界面,并且通过远距离静电相互作用使其稳定。中间体探索了广泛的构象分布;这种分布在最终建筑群中变得更加受限,并受到SRP货物的进一步管制。这些结果表明了蛋白相互作用的漏斗形能量格局,并且它们为理解瞬时中间体在蛋白组装和生物调节中的作用提供了框架。

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  • 作者单位

    Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125;

    Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125;

    Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125;

    Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125,Beckman Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125;

    Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125;

    Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125;

    Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125,Beckman Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125;

    Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125,Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125;

    Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125;

  • 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

    epr spectroscopy; fluorescence spectroscopy; molecular recognition; protein targeting; gtpases;

    机译:epr光谱;荧光光谱;分子识别;蛋白质靶向;gtpases;

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