Solution structure of DFF40 and DFF45 N-terminal domain complex and mutual chaperone activity of DFF40 and DFF45
Solution structure of DFF40 and DFF45 N-terminal domain complex and mutual chaperone activity of DFF40 and DFF45
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DOI：
10.1073/pnas.111145098
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发表时间：
2001-05
影响因子：
11.1
通讯作者：
P. Zhou;A. Lugovskoy;J. McCarty;Peng Li;G. Wagner
中科院分区：
文献类型：
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作者：
P. Zhou;A. Lugovskoy;J. McCarty;Peng Li;G. Wagner
凋亡 DNA 片段化是由 caspase 激活的 DNA 片段化因子 (DFF)40 介导的。 DFF40 的表达和折叠需要 DFF45 的存在，DFF45 在执行 caspase 激活 DFF40 之前也充当核酸酶抑制剂。两种蛋白质的 N 端结构域 (NTD) 是同源的，它们的相互作用在这个双组分系统的正常运作中起着关键作用。在这里，我们报告单独的 DFF45 的 NTD 在溶液中是非结构化的，并且在与 DFF40 NTD 结合时诱导其折叠。因此，两种蛋白质的折叠调节 DFF40/DFF45 复合物的形成。本文报道的 DFF40 和 DFF45 NTD 之间的异二聚复合物的溶液结构表明，相互陪伴包括形成广泛的分子间相互作用网络，该网络将疏水簇埋藏在界面内，并被分子间盐桥包围。
Apoptotic DNA fragmentation is mediated by a caspase-activated DNA fragmentation factor (DFF)40. Expression and folding of DFF40 require the presence of DFF45, which also acts as a nuclease inhibitor before DFF40 activation by execution caspases. The N-terminal domains (NTDs) of both proteins are homologous, and their interaction plays a key role in the proper functioning of this two-component system. Here we report that the NTD of DFF45 alone is unstructured in solution, and its folding is induced upon binding to DFF40 NTD. Therefore, folding of both proteins regulates the formation of the DFF40/DFF45 complex. The solution structure of the heterodimeric complex between NTDs of DFF40 and DFF45 reported here shows that the mutual chaperoning includes the formation of an extensive network of intermolecular interactions that bury a hydrophobic cluster inside the interface, surrounded by intermolecular salt bridges.