UHRF2与增殖细胞核抗原相互作用分子机制的结构洞察
Structure insights into the molecular mechanism of the interaction between UHRF2 and PCNA.
作者信息
Chen Wanbiao, Wu Minhao, Hang Tianrong, Wang Chengliang, Zhang Xuan, Zang Jianye
机构信息
Hefei National Laboratory for Physical Sciences at Microscale CAS Center for Excellence in Biomacromolecules, Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, China.
Hefei National Laboratory for Physical Sciences at Microscale CAS Center for Excellence in Biomacromolecules, Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, China.
出版信息
Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):575-580. doi: 10.1016/j.bbrc.2017.09.102. Epub 2017 Sep 23.
UHRF2 (Ubiquitin-like with PHD and ring finger domains 2) is an E3 ubiquitin ligase that plays important roles in DNA methylation, histone modifications and cell cycle regulation by interacting with multiple epigenetic or cell-cycle related proteins. Previous studied have identified PCNA (Proliferating cell nuclear antigen) as an interacting partner of UHRF2 by using the antibody microarray. However, the molecular mechanism and the function of UHRF2-PCNA interaction remains unclear. Here, we report the complex structure of PCNA and the peptide (NEILQTLLDLFFPGYSK) derived from UHRF2 that contains a PIP box. Structural analysis combined with mutagenesis experiments provide the molecular basis for the recognition of UHRF2 by PCNA via PIP-box.
UHRF2（含PHD和环指结构域的类泛素蛋白2）是一种E3泛素连接酶，通过与多种表观遗传或细胞周期相关蛋白相互作用，在DNA甲基化、组蛋白修饰和细胞周期调控中发挥重要作用。先前的研究通过抗体微阵列鉴定出PCNA（增殖细胞核抗原）是UHRF2的相互作用伴侣。然而，UHRF2与PCNA相互作用的分子机制和功能仍不清楚。在此，我们报道了PCNA与源自UHRF2的包含PIP框的肽（NEILQTLLDLFFPGYSK）的复合物结构。结构分析与诱变实验相结合，为PCNA通过PIP框识别UHRF2提供了分子基础。
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