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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structural Plasticity Of An Acid-activated Chaperone Allows Promiscuous Substrate Binding
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Structural Plasticity Of An Acid-activated Chaperone Allows Promiscuous Substrate Binding

机译:酸活化伴侣的结构可塑性允许混杂的底物结合。

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摘要

HdeA has been shown to prevent acid-induced aggregation of proteins. With a mass of only 9.7 kDa, HdeA is one of the smallest chaperones known. Unlike other molecular chaperones, which are typically complex, multimeric ATP-dependent machines, HdeA is known to undergo an acid-induced dimer to monomer transition and functions at low pH as a disordered monomer without the need for energy factors. Thus, HdeA must possess features that allow it to bind substrates and regulate substrate affinity in a small and energy-independent package. To understand better how HdeA accomplishes this, we studied the conformational changes that accompany a shift to low pH and substrate binding. We find that the acid-induced partial unfolding and monomerization that lead to HdeA activation occur very rapidly (k >3.5 s~(-1)). Activation exposes the hydrophobic dimer interface, which we found to be critical for substrate binding. We show by intramolecular FRET that the partially unfolded character of active HdeA allows the chaperone to adopt different conformations as required for the recognition and high-affinity binding of different substrate proteins. These efficient adaptations help to explain how a very small protein is rapidly activated and can bind a broad range of substrate proteins in a purely pH-regulated manner.
机译:HdeA已显示可防止酸诱导的蛋白质聚集。 HdeA的质量仅为9.7 kDa,是已知的最小的分子伴侣之一。与通常是复杂的多聚ATP依赖性机器的其他分子伴侣不同,HdeA已知会经历酸诱导的二聚体向单体的转变,并在低pH下作为无序单体起作用,而无需能源因素。因此,HdeA必须具有允许其以小的且与能量无关的包装形式结合底物并调节底物亲和力的特征。为了更好地了解HdeA如何做到这一点,我们研究了伴随向低pH和底物结合转变的构象变化。我们发现酸诱导的局部解折叠和单体化导致HdeA活化发生得非常快(k> 3.5 s〜(-1))。活化暴露了疏水性二聚体界面,我们发现这对底物结合至关重要。我们通过分子内FRET表明,活性HdeA的部分展开特征使分子伴侣能够根据识别和高亲和力结合不同底物蛋白所需采取不同的构象。这些有效的改编有助于解释非常小的蛋白质是如何快速激活的,并且可以以纯pH调节的方式结合多种底物蛋白质。

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  • 作者单位

    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Ml 48109;

    Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Ml 48109;

    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Ml 48109;

    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Ml 48109;

    Biophysics Research Division and Department of Biological Chemistry University of Michigan, Ann Arbor, Ml 48109;

    Biophysics Research Division and Department of Biological Chemistry University of Michigan, Ann Arbor, Ml 48109;

    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Ml 48109;

    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Ml 48109 Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Ml 48109;

  • 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

    hdea; periplasm; posttranslational regulation;

    机译:人类;周质;翻译后调控;

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