Insights into the amyloid folding problem from solid-state NMR.
Insights into the amyloid folding problem from solid-state NMR.
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DOI：
10.1021/bi027378p
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发表时间：
2003-02
期刊：
影响因子：
2.9
通讯作者：
R. Tycko
中科院分区：
文献类型：
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作者：
R. Tycko
测量。目前生物医学界对淀粉样纤维的兴趣源于这样一个事实，即淀粉样纤维沉积在所谓的淀粉样病的受影响器官中(1)。几种淀粉样病，包括阿尔茨海默病、2型糖尿病、传染性海绵状脑病和帕金森氏病，构成了主要的公共卫生问题。淀粉样蛋白沉积在这些疾病中的确切作用尚未确定，但淀粉样蛋白沉积可能至少是其病因的一个贡献因素(2，3)。在生物物理学和生化界，对淀粉样纤维的兴趣还源于观察到淀粉样纤维似乎是一种普通多肽链(4，5)的稳定结构状态，以及对这一观察结果缺乏全面的解释。在EM图像水平上，由具有不相关序列的多肽和蛋白质形成的淀粉样纤维至少看起来相似，如果不相同的话。因此，淀粉样蛋白纤维化带来了一个与常见的蛋白质折叠问题相反的问题。在蛋白质折叠问题中，人们试图理解蛋白质的不同三维结构是如何由它们的氨基酸序列唯一地确定的，而在淀粉样折叠问题中，人们试图理解单个结构如何对于大量不相关的序列是共同的。
measurements. Current interest in amyloid fibrils in the biomedical community stems from the fact that amyloid fibrils deposit in the affected organs of the so-called amyloid diseases ( 1). Several amyloid diseases, including Alzheimer’s disease, type 2 diabetes, transmissible spongiform encephalopathies, and Parkinson’s disease, constitute major public health problems. The precise role of amyloid deposits in these diseases has not been settled, but amyloid deposition is likely to be at least a contributing factor to their etiology ( 2, 3). In the biophysical and biochemical communities, interest in amyloid fibrils additionally stems from the observation that the amyloid fibril appears to be a stable structural state of a generic polypeptide chain ( 4, 5) and from the lack of a comprehensive explanation for this observation. At the level of EM images, amyloid fibrils formed by peptides and proteins with unrelated sequences appear at least similar, if not identical. Thus, amyloid fibrillization poses a problem that is opposite to the familiar protein folding problem. Whereas in the protein folding problem one seeks to understand how the diverse three-dimensional structures of proteins are determined uniquely by their amino acid sequences, in the amyloid folding problem one seeks to understand how a single structure can be common to a great many unrelated sequences.