An amyloid-forming segment of β2-microglobulin suggests a molecular model for the fibril
An amyloid-forming segment of β2-microglobulin suggests a molecular model for the fibril
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DOI：
10.1073/pnas.0403756101
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发表时间：
2004-07-20
影响因子：
11.1
通讯作者：
Eisenberg, D
中科院分区：
文献类型：
--
作者：
Ivanova, MI;Sawaya, MR;Eisenberg, D
在患有透析相关淀粉样变性的人类中，β2-微球蛋白（β2M）以淀粉样蛋白的形式沉积；然而，β2M 淀粉样蛋白在小鼠体内尚不清楚。人和小鼠的 beta2M 序列有 70% 相同，但有一个七残基肽，其中六个残基不同。这种来自人 beta2M 的肽在体外形成淀粉样蛋白，而小鼠肽则不会。用人肽替代小鼠序列中的对应肽会导致体外淀粉样蛋白的形成。这些结果表明，人 beta2M 的七个残基片段足以将 beta2M 转化为淀粉样蛋白状态，并且特定的残基相互作用对于该转化至关重要。这些观察结果与提出的 beta2M 淀粉样蛋白拉链脊柱模型一致，其中原纤维的脊柱由无水 P-片组成。
In humans suffering from dialysis-related amyloidosis, the protein beta2-microglobulin (beta2M) is deposited as an amyloid; however, an amyloid of beta2M is unknown in mice. beta2M sequences from human and mouse are 70% identical, but there is a seven-residue peptide in which six residues differ. This peptide from human beta2M forms amyloid in vitro, whereas the mouse peptide does not. Substitution of the human peptide for its counterpart in the mouse sequence results in the formation of amyloid in vitro. These results show that a seven-residue segment of human beta2M is sufficient to convert beta2M to the amyloid state, and that specific residue interactions are crucial to the conversion. These observations are consistent with a proposed Zipper-spine model for beta2M amyloid, in which the spine of the fibril consists of an anhydrous P-sheet.