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Structural basis for the antifolding activity of a molecular chaperone

机译:分子伴侣的抗折叠活性的结构基础

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摘要

Molecular chaperones act on non-native proteins in the cell to prevent their aggregation, premature folding or misfolding. Different chaperones often exert distinct effects, such as acceleration or delay of folding, on client proteins via mechanisms that are poorly understood. Here we report the solution structure of SecB, a chaperone that exhibits strong antifolding activity, in complex with alkaline phosphatase and maltose-binding protein captured in their unfolded states. SecB uses long hydrophobic grooves that run around its disk-like shape to recognize and bind to multiple hydrophobic segments across the length of non-native proteins. The multivalent binding mode results in proteins wrapping around SecB. This unique complex architecture alters the kinetics of protein binding to SecB and confers strong antifolding activity on the chaperone. The data show how the different architectures of chaperones result in distinct binding modes with non-native proteins that ultimately define the activity of the chaperone.
机译:分子伴侣对细胞中的非天然蛋白质起作用,以防止其聚集,过早折叠或错误折叠。不同的分子伴侣通常通过不了解的机制对客户蛋白质产生不同的作用,例如加速或折叠延迟。在这里,我们报告了SecB的溶液结构,一种具有强抗折叠活性的分子伴侣,与碱性磷酸酶和麦芽糖结合蛋白结合处于其未折叠状态时,具有很强的抗折叠活性。 SecB使用长的疏水性沟槽围绕其盘状形状延伸,以识别并结合跨非天然蛋白长度的多个疏水性片段。多价结合模式导致蛋白​​质包裹在SecB周围。这种独特的复杂结构改变了蛋白质与SecB结合的动力学,并赋予了伴侣分子强大的抗折叠活性。数据显示了不同的分子伴侣结构如何导致与非天然蛋白的独特结合模式,从而最终定义了分子伴侣的活性。

著录项

  • 来源
    《Nature》 |2016年第7619期|202-206|共5页
  • 作者单位

    Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA;

    Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA;

    Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA;

    Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 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
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