Laboratory of Molecular Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Phys Chem Chem Phys. 2011 Dec 7;13(45):20066-75. doi: 10.1039/c1cp21376h. Epub 2011 Oct 12.
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.
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。
