Crystal structure of the N-terminal region of human Topoisomerase IIβ binding protein 1
Crystal structure of the N-terminal region of human Topoisomerase IIβ binding protein 1
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DOI：
10.1016/j.bbrc.2010.09.066
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发表时间：
2010-10-22
影响因子：
3.1
通讯作者：
Jiang, Tao
中科院分区：
文献类型：
--
作者：
Huo, Yan-gao;Bai, Lin;Jiang, Tao
人DNA拓扑异构酶II β结合蛋白1（TopBP 1）是一种调节蛋白，在DNA损伤应答中起重要作用。TopBP 1的N-末端区域包含预测的BRCA 1-羧基末端（BRCT）结构域1和2，与细胞周期检查点钳Rad 9-Hus 1-Rad 1复合物的组分Rad 9结合。在这里，我们报告了TopBP 1 N-末端区域（残基1-290）的晶体结构，分辨率为2.4埃。有趣的是，除了预测的串联BRCT 1 -2重复序列（残基103-284），残基7-98形成了以前未报道的BRCT结构域（这里，BRCT 0）。与BRCT 1和BRCT 2相反，BRCT 1和BRCT 2在表面口袋内具有常规的磷酸肽结合残基，BRCT 0中的相应口袋在很大程度上是疏水性的。结构比较与肽结合研究表明，串联BRCT 1 -2结构域是磷酸化的Ser 387在Rad 9的结合区域。(C)2010年爱思唯尔公司All rights reserved.
Human DNA Topoisomerase II beta binding protein 1 (TopBP1) is a modulating protein that plays an essential role in the response to DNA damage. The N-terminal region of TopBP1, which contains predicted BRCA1-carboxy terminal (BRCT) domains 1 and 2, binds to Rad9, a component of the cell cycle checkpoint clamp Rad9-Hus1-Rad1 complex. Here, we report the crystal structure of the TopBP1 N-terminal region (residues 1-290) at 2.4 angstrom resolution. Interestingly, in addition to the predicted tandem BRCT1-2 repeats (residues 103-284), residues 7-98 form a previously unreported BRCT domain (here, BRCT0). In contrast to both BRCT1 and BRCT2, which possess the conventional phosphopeptide binding residues within a surface pocket, the corresponding pocket in BRCT0 is largely hydrophobic. Structural comparisons together with peptide binding studies indicate that the tandem BRCT1-2 domains are the binding region for phosphorylated Ser387 in Rad9. (C) 2010 Elsevier Inc. All rights reserved.