Structure and mechanism of protein stability sensors: chaperone activity of small heat shock proteins.

Structure and mechanism of protein stability sensors: chaperone activity of small heat shock proteins.
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蛋白质稳定传感器的结构和机制:小热激蛋白的伴侣活性。

DOI:
10.1021/bi900212j
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发表时间:
2009-05-12
期刊:
影响因子:
2.9
通讯作者:
Stewart, Phoebe L.
Stewart, Phoebe L.
中科院分区:
生物学3区
文献类型:
--
作者:
Mchaourab, Hassane S.;Godar, Jared A.;Stewart, Phoebe L.

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小热休克蛋白(sHSP)是一种非常多样化的分子伴侣,具有其他蛋白质超家族无与伦比的结构可塑性。在没有化学能输入的情况下,这些稳定性传感器可以灵敏地识别和结合不稳定的蛋白质,即使在没有严重错误折叠的情况下。细胞条件调节对客户蛋白的亲和力,允许严格控制sHSP伴侣蛋白容量的开关和调节。这种调控的扰动,通过化学修饰或突变,直接导致各种疾病状态。这篇综述探讨了sHSP寡聚体柔韧性的结构基础,以及在描述sHSP活性的一组三个耦合热力学平衡模型的背景下相应的功能后果。由于目前的研究阐明了sHSP在其传统的分子伴侣功能之外的许多新的生理作用,这样的概念框架为描述这些在生理和病理过程中的新兴功能提供了良好的基础。
Small heat shock proteins (sHSP) are a remarkably diverse group of molecular chaperones possessing a degree of structural plasticity unparalleled in other protein superfamilies. In the absence of chemical energy input, these stability sensors can sensitively recognize and bind destabilized proteins, even in the absence of gross misfolding. Cellular conditions regulate affinity towards client proteins allowing tightly controlled switching and tuning of sHSP chaperone capacity. Perturbations of this regulation, through chemical modification or mutation, directly lead to a variety of diseased states. This review explores the structural basis of sHSP oligomeric flexibility and the corresponding functional consequences in the context of a model describing sHSP activity with a set of three coupled thermodynamic equilibria. As current research illuminates many novel physiological roles for sHSP outside of their traditional duties as molecular chaperones, such a conceptual framework provides a sound foundation to describe these emerging functions in physiological and pathological processes.
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期刊: FEBS LETTERS
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