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首页> 外文期刊>Coordination chemistry reviews >Metal ions as modulators of protein conformation and misfolding in neurodegeneration
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Metal ions as modulators of protein conformation and misfolding in neurodegeneration

机译：金属离子作为神经变性中蛋白质构象和错误折叠的调节剂

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摘要

Protein misfolding and conformational changes are a cornerstone of neurodegenerative diseases involving formation and deposition of toxic protein oligomers. Although mutations favor protein aggregation, physiological factors such as labile metal ions within the cellular environment are likely to play a role. Metal ions such as calcium, zinc and copper are key players in brain neurobiology, their homeostasis is altered in most neurodegenerative conditions and they are found within proteinaceous inclusions from patients. In this review we will elucidate the intricate interplay between protein (mis)folding and metal ions, discussing how metals modulate protein folding and influence protein energetics, with specific attention on conformational changes and structural fluctuations. In particular, the influence of metal ion dyshomeostasis during neurodegeneration and the effects of the unique physical and chemical properties at the synaptic environment will be discussed in the context of protein deposition. These interactions will be illustrated by specific examples of proteins involved in neurodegenerative diseases including α-synudein, tau, superoxide dismutase 1, the prion protein and the amyloid-p peptide. With this approach we aim to systematize the effects of metal ions on protein conformers and illustrate pathways through which they modulate protein aggregation, under different conceptual mechanisms that bridge protein structure, metallochemistry and neurobiology.
机译：蛋白质错误折叠和构象变化是神经退行性疾病的基石，涉及有毒蛋白质低聚物的形成和沉积。尽管突变有利于蛋白质聚集，但是诸如细胞环境中不稳定的金属离子之类的生理因素可能会发挥作用。金属离子（例如钙，锌和铜）是大脑神经生物学的关键因素，它们的稳态在大多数神经退行性疾病中都会改变，并且存在于患者的蛋白质内含物中。在这篇综述中，我们将阐明蛋白质（错误）折叠与金属离子之间的复杂相互作用，讨论金属如何调节蛋白质折叠并影响蛋白质能量学，并特别关注构象变化和结构波动。特别是，将在蛋白质沉积的背景下讨论神经变性过程中金属离子动态平衡的影响以及突触环境下独特的物理和化学性质的影响。这些相互作用将通过涉及神经退行性疾病的蛋白质的具体例子进行说明，这些蛋白质包括α-突触核蛋白，tau，超氧化物歧化酶1，pr病毒蛋白和淀粉样蛋白p肽。通过这种方法，我们旨在将金属离子对蛋白质构象异构体的影响系统化，并说明它们在桥接蛋白质结构，金属化学和神经生物学的不同概念机制下调节蛋白质聚集的途径。

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  • 来源
    《Coordination chemistry reviews》 |2012年第20期|p.2253-2270|共18页
  • 作者

    Sonia S. Leal; Hugo M. Botelho; Claudio M. Gomes;

  • 作者单位

    Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa Av. da Republica, 2780-157 Oeiras, Portugal;

    Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa Av. da Republica, 2780-157 Oeiras, Portugal;

    Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa Av. da Republica, 2780-157 Oeiras, Portugal;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    metals; protein folding; copper; zinc; calcium; neurodegeneration; amyloid;

    机译：金属;蛋白质折叠铜;锌钙;神经变性淀粉样蛋白;

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