蛋白质在超分子自我组合的边缘进化
Hector Garcia-Seisdedos1, Charly Empereur-Mot1, Nadav Elad2
1Department of Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Nature
|August 8, 2017
概括
当突变增加表面疏水性时,对称的蛋白质复合体可以形成有害的纤维. 这项研究揭示了预测组装的几何"热点",为疾病和纳米材料设计提供了洞察力.
科学领域:
- 生物化学
- 结构生物学
- 分子生物学
背景情况:
- 蛋白质自组成对称的复合体是整个生命中常见的.
- 蛋白质对称性可能导致有害的聚合, 正如在状细胞疾病中所见.
研究的目的:
- 在对称复合体中研究突变诱导的蛋白质自组合的普遍性.
- 探索蛋白质结构几何学与超分子组合之间的关系.
- 识别可预测的组装热点并了解保护机制.
主要方法:
- 在12个不同的对称蛋白质复合体中引入点突变以增加表面疏水性.
- 在Saccharomyces cerevisiae中表达的突变,以观察体内组合.
- 使用生物物理测量和电子显微镜来描述组件.
- 进行突变的结构分析和对称复合体的大数据集.
主要成果:
- 所有测试的对称复合体在体外和体内突变后形成了超分子组合.
- 在四例体内,单点突变引发了长纤维的形成.
- 突变物在它们的折叠状态中自我组装,与粉样蛋白形成不同.
- 通过结构可预测的超分子组合的确定几何"热点".
- 发现水性残留物会化学缓冲这些几何热点, 防止错误组装.
结论:
- 点突变经常会诱导折叠的蛋白质形成更高阶的结构.
- 错误组装的可能性被负选择所抵消.
- 这种现象可以用来设计细胞内纳米材料.
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