淀粉样蛋白的阴阳两面：来自 α-突触核蛋白和 Pmel17 重复结构域的见解。
The yin and yang of amyloid: insights from α-synuclein and repeat domain of Pmel17.
机构信息
Laboratory of Molecular Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
出版信息
Phys Chem Chem Phys. 2011 Dec 7;13(45):20066-75. doi: 10.1039/c1cp21376h. Epub 2011 Oct 12.
Abstract
Amyloid has been traditionally viewed in the context of disease. However, the emerging concept of 'functional amyloid' has taken a new direction into how we view amyloid. Recent studies have identified amyloid fibrils ranging from bacteria to humans that have a beneficial role, instead of being associated with a misfolded state that has been implicated in diseases such as Alzheimer's, Parkinson's and prion diseases. Here, we review our work on two human amyloidogenic polypeptides, one associated with Parkinson's disease, α-synuclein (α-syn), and the other important for melanin synthesis, the repeat domain (RPT) from Pmel17. Particularly, we focused our attention on spectroscopic studies of protein conformation and dynamics and their impact on α-syn amyloid formation and for RPT, we discussed the strict pH dependence of amyloid formation and its role in melanin biosynthesis.
摘要
淀粉样蛋白一直以来都是从疾病的角度来进行研究的。然而，“功能性淀粉样蛋白”这一新兴概念为我们研究淀粉样蛋白提供了一个全新的视角。最近的研究发现，从细菌到人类的淀粉样纤维都具有有益的作用，而不是与折叠错误状态相关，折叠错误状态与阿尔茨海默病、帕金森病和朊病毒病等疾病有关。在这里，我们回顾了我们在两个人类淀粉样蛋白多肽方面的工作，一个与帕金森病有关，即α-突触核蛋白（α-syn），另一个对黑色素合成很重要，即 Pmel17 的重复结构域（RPT）。特别是，我们专注于蛋白质构象和动力学的光谱研究及其对α-syn 淀粉样蛋白形成的影响，对于 RPT，我们讨论了淀粉样蛋白形成的严格 pH 依赖性及其在黑色素生物合成中的作用。
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