Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
Structure. 2012 Jul 3;20(7):1212-22. doi: 10.1016/j.str.2012.04.012. Epub 2012 May 31.
Knowledge of the architecture of DNA ligase IV (LigIV) and interactions with XRCC4 and XLF-Cernunnos is necessary for understanding its role in the ligation of double-strand breaks during nonhomologous end joining. Here we report the structure of a subdomain of the nucleotidyltrasferase domain of human LigIV and provide insights into the residues associated with LIG4 syndrome. We use this structural information together with the known structures of the BRCT/XRCC4 complex and those of LigIV orthologs to interpret small-angle X-ray scattering of LigIV in complex with XRCC4 and size exclusion chromatography of LigIV, XRCC4, and XLF-Cernunnos. Our results suggest that the flexibility of the catalytic region is limited in a manner that affects the formation of the LigIV/XRCC4/XLF-Cernunnos complex.
了解 DNA 连接酶 IV（LigIV）的结构及其与 XRCC4 和 XLF-Cernunnos 的相互作用，对于理解其在非同源末端连接过程中双链断裂连接中的作用是必要的。在这里，我们报告了人 LigIV 的核核苷酸转移酶结构域的一个亚结构域的结构，并提供了与 LIG4 综合征相关的残基的见解。我们使用这种结构信息，以及已知的 BRCT/XRCC4 复合物的结构和 LigIV 同源物的结构，来解释 LigIV 与 XRCC4 形成复合物的小角度 X 射线散射和 LigIV、XRCC4 和 XLF-Cernunnos 的分子筛层析。我们的结果表明，催化区域的灵活性受到限制，这会影响 LigIV/XRCC4/XLF-Cernunnos 复合物的形成。
