Crystal structure of an Xrcc4-DNA ligase IV complex
Crystal structure of an Xrcc4-DNA ligase IV complex
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DOI：
10.1038/nsb725
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发表时间：
2001-12-01
期刊：
影响因子：
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通讯作者：
Pellegrini, L
中科院分区：
文献类型：
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作者：
Sibanda, BL;Critchlow, SE;Pellegrini, L
两种蛋白质Xrcc 4和DNA连接酶IV的复合物在DNA非同源末端连接（NHEJ）中起着重要作用，这是双链断裂修复和V（D）J重组所需的细胞功能。在这里，我们报告的晶体结构的人Xrcc 4结合到一个多肽，对应于DNA连接酶IV序列连接其两个BRCA 1的C-末端（BRCT）域。在复合物中，单个连接酶链不对称地结合到Xrcc 4二聚体。Xrcc 4的螺旋尾部相对于未复合的蛋白质经历了实质性的构象变化，形成了在连接酶结合时解旋的卷曲螺旋，导致了平坦的相互作用表面。被广泛的疏水接触包围的带电氢键的掩埋网络解释了所观察到的相互作用的紧密性。在两种蛋白质之间的界面残基的强烈保守性提供了证据，表明在整个进化过程中，所观察到的相互作用模式一直保持在NHEJ中。
A complex of two proteins, Xrcc4 and DNA ligase IV, plays a fundamental role in DNA non-homologous end joining (NHEJ), a cellular function required for double-strand break repair and V(D)J recombination. Here we report the crystal structure of human Xrcc4 bound to a polypeptide that corresponds to the DNA ligase IV sequence linking its two BRCA1 C-terminal (BRCT) domains. In the complex, a single ligase chain binds asymmetrically to an Xrcc4 dimer. The helical tails of Xrcc4 undergo a substantial conformational change relative to the uncomplexed protein, forming a coiled coil that unwinds upon ligase binding, leading to a flat interaction surface. A buried network of charged hydrogen bonds surrounded by extensive hydrophobic contacts explains the observed tightness of the interaction. The strong conservation of residues at the interface between the two proteins provides evidence that the observed mode of interaction has been maintained in NHEJ throughout evolution.