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首页> 外文期刊>Biochemistry >BRCT domain interactions in the heterodimeric DNA repair protein XRCC1-DNA ligase III
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BRCT domain interactions in the heterodimeric DNA repair protein XRCC1-DNA ligase III

机译：异二聚体DNA修复蛋白XRCC1-DNA连接酶III中的BRCT域相互作用

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摘要

Proteins involved in DNA repair, or its coordination with DNA replication and mitosis through cell cycle checkpoints, are vital in the concerted cellular response to DNA damage that maintains the integrity of the genome. The “BRCT” domain (BRCA1 carboxy terminal) was noted as a putative protein— protein interaction motif in the breast cancer suppressor gene, BRCA], and subsequently identified in over 50 proteins involved in DNA repair, recombination, or cell cycle control. The heterodimer of the DNA repair proteins, XRCC1 and DNA ligase III, was the first example of a functional interaction via BRCT modules. The only three-dimensional crystal structure of a BRCT domain was solved for this region of XRCC 1. Key amino acid residues mediating the interaction with DNA ligase III were identified here by targeted mutagenesis of the XRCC I BRCT domain. The consequences of these mutations on protein folding were assessed. A structural model of the DNA ligase III BRCT domain was constructed and similarly tested by mutation of corresponding residues required for the interaction with XRCC1. These data identify the XRCC I-DNA ligase III heterodimer interface and provide the first demonstration of the surface contacts coordinating a functional BRCT—BRCT protein interaction.
机译：参与DNA修复的蛋白质，或通过细胞周期检查点与DNA复制和有丝分裂相协调的蛋白质，在协调一致的细胞对DNA损伤的反应（维持基因组完整性）中至关重要。 “ BRCT”结构域（BRCA1羧基末端）在乳腺癌抑制基因[BRCA]中被认为是推定的蛋白质-蛋白质相互作用基序，随后在涉及DNA修复，重组或细胞周期控制的50多种蛋白质中被鉴定出来。 DNA修复蛋白XRCC1和DNA连接酶III的异二聚体是通过BRCT模块进行功能相互作用的第一个例子。对于XRCC 1区域，解决了BRCT结构域的唯一三维晶体结构。通过靶向诱变XRCC I BRCT结构域，确定了介导与DNA连接酶III相互作用的关键氨基酸残基。评估了这些突变对蛋白质折叠的影响。构建了DNA连接酶III BRCT结构域的结构模型，并通过突变与XRCC1相互作用所需的相应残基进行了相似的测试。这些数据确定了XRCC I-DNA连接酶III异二聚体界面，并首次证明了协调功能性BRCT-BRCT蛋白相互作用的表面接触。

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