Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
FEBS Lett. 2011 Dec 15;585(24):3874-9. doi: 10.1016/j.febslet.2011.10.045. Epub 2011 Nov 3.
Human Pax2 transactivation domain-interacting protein (hPTIP), containing six BRCT domains, is an essential protein required for the IR induced DDR process with an unclear role. Here we report that the tandem BRCT5-BRCT6 domain of hPTIP recognizes the γH2AX tail, and this interaction depends on the phosphorylation of H2AX Ser139 and binding with the carboxyl ending peptide to the aminoacyl ending peptide. The 2.15 Å crystal structure of hPTIP BRCT5/6-γH2AX complex and mutation analysis provide molecular evidence for direct interactions between PTIP and γH2AX. This interaction proffers a new clue to identify the role of PTIP in DDR pathways.
人类 Pax2 转录激活结构域相互作用蛋白（hPTIP），含有六个 BRCT 结构域，是 IR 诱导 DDR 过程中必需的蛋白质，但作用尚不明确。我们报告称 hPTIP 的串联 BRCT5-BRCT6 结构域识别 γH2AX 尾巴，这种相互作用依赖于 H2AX Ser139 的磷酸化和与羧基末端肽结合到氨酰末端肽。hPTIP BRCT5/6-γH2AX 复合物的 2.15Å 晶体结构和突变分析为 PTIP 和 γH2AX 之间的直接相互作用提供了分子证据。这种相互作用为确定 PTIP 在 DDR 途径中的作用提供了新的线索。
