Mapping the core of the β2-microglobulin amyloid fibril by H/D exchange
Mapping the core of the β2-microglobulin amyloid fibril by H/D exchange
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DOI：
10.1038/nsb792
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发表时间：
2002-05-01
期刊：
影响因子：
--
通讯作者：
Goto, Y
中科院分区：
文献类型：
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作者：
Hoshino, M;Katou, H;Goto, Y
尽管做了许多努力，但缺乏淀粉样蛋白原纤维的详细结构信息阻碍了对其形成机制的阐明。在这里，我们描述了一种在单残基分辨率下表征β(2)-微球蛋白淀粉样蛋白原纤维构象灵活性的新方法，该方法使用酰胺质子的H/D交换结合核磁共振分析。结果表明，分子中部的大部分残基，包括天然结构中的环区，形成了一个刚性的β -片核，而N端和c端被排除在这个核之外。广泛的氢键β -片核解释了淀粉样蛋白原纤维的显著刚性和稳定性。本方法可用于获取各种淀粉样蛋白原纤维的残基特异性构象信息，尽管它不能提供高分辨率的三维结构。
Despite numerous efforts, the lack of detailed structural information on amyloid fibrils has hindered clarification of the mechanism of their formation. Here, we describe a novel procedure for characterizing the conformational flexibility of beta(2)-microglobulin amyloid fibrils at single-residue resolution that uses H/D exchange of amide protons combined with NMR analysis. The results indicate that most residues in the middle region of the molecule, including the loop regions in the native structure, form a rigid beta-sheet core, whereas the the N- and C-termini are excluded from this core. The extensively hydrogen-bonded beta-sheet core explains the remarkable rigidity and stability of amyloid fibrils. The present method could be used to obtain residue-specific conformational information of various amyloid fibrils, even though it does not provide a high resolution three-dimensional structure.