Intermolecular disulfide linkages are not required for transthyretin amyloid fibril formation in vitro.
Intermolecular disulfide linkages are not required for transthyretin amyloid fibril formation in vitro.
复制标题
体外转甲状腺素蛋白淀粉样原纤维的形成不需要分子间二硫键。
DOI：
10.1006/bbrc.1993.2495
复制
发表时间：
1993
影响因子：
3.1
通讯作者：
Kelly,JW
中科院分区：
文献类型：
--
作者：
McCutchen,SL;Kelly,JW
通过比较野生型TTR与不能形成二硫键的Cys-10-Ala TTR，研究了分子间二硫键在甲状腺素运载蛋白（TFR）淀粉样蛋白原纤维形成中的作用。Cys-10-Ala变体在酸性变性条件下表现出与野生型蛋白质相等的四级结构稳定性。Cys-10-Ala和野生型TTR均通过部分酸变性转化为淀粉样纤维。在野生型淀粉样蛋白原纤维的情况下，没有分子间二硫键形成的证据。这些结果与最近提出的强调TTR淀粉样蛋白原纤维形成中分子间二硫键的重要性的模型不一致，但与依赖于通过酸介导的构象变化而可能实现的非共价季铵接触的模型一致。
The role of intermolecular disulfide linkages in transthyretin (TFR) amyloid fibril formation was investigated by comparing wild type TTR to Cys-10-Ala TTR which is incapable of disulfide formation. The Cys-10-Ala variant exhibits quaternary structural stability equal to the wild type protein under acidic denaturing conditions. Both Cys-10-Ala and wild type TTR were converted into amyloid fibrils by partial acid denaturation. There was no evidence of intermolecular disulfide formation in the case of wild type amyloid fibrils. These results are inconsistent with a recently proposed model stressing the importance of intermolecular disulfide linkages in TTR amyloid fibril formation, but are consistent with a model relying on noncovalent quaternary contacts made possible through an acid-mediated conformational change.