对异质核糖核蛋白A2/B1同源二聚化及DNA识别的结构洞察
Structural Insight Into hnRNP A2/B1 Homodimerization and DNA Recognition.
作者信息
Liu Yue, Abula Abudureyimu, Xiao Haonan, Guo Hangtian, Li Tinghan, Zheng Le, Chen Biqing, Nguyen Henry C, Ji Xiaoyun
机构信息
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Institute of Viruses and Infectious Diseases, Chemistry and Biomedicine Innovation Center (ChemBIC), Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, People's Republic of China.
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Institute of Viruses and Infectious Diseases, Chemistry and Biomedicine Innovation Center (ChemBIC), Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, People's Republic of China; School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, Xinjiang 830054, People's Republic of China.
出版信息
J Mol Biol. 2023 Feb 1;435(3):167920. doi: 10.1016/j.jmb.2022.167920. Epub 2022 Dec 14.
Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) has been identified as a nuclear DNA sensor. Upon viral infection, hnRNP A2/B1 recognizes pathogen-derived DNA as a homodimer, which is a prerequisite for its translocation to the cytoplasm to activate the interferon response. However, the DNA binding mechanism inducing hnRNP A2/B1 homodimerization is unknown. Here, we show the crystal structure of the RNA recognition motif (RRM) of hnRNP A2/B1 in complex with a U-shaped ssDNA, which mediates the formation of a newly observed protein dimer. Our biochemical assays and mutagenesis studies confirm that the hnRNP A2/B1 homodimer forms in solution by binding to pre-generated ssDNA or dsDNA with a U-shaped bulge. These results depict a potential functional state of hnRNP A2/B1 in antiviral immunity and other cellular processes.
异质性细胞核核糖核蛋白A2/B1（hnRNP A2/B1）已被鉴定为一种细胞核DNA传感器。在病毒感染时，hnRNP A2/B1作为同源二聚体识别病原体衍生的DNA，这是其转运至细胞质以激活干扰素反应的前提条件。然而，诱导hnRNP A2/B1同源二聚化的DNA结合机制尚不清楚。在此，我们展示了与U形单链DNA结合的hnRNP A2/B1的RNA识别基序（RRM）的晶体结构，该结构介导了新观察到的蛋白质二聚体的形成。我们的生化分析和诱变研究证实，hnRNP A2/B1同源二聚体通过与预先形成的具有U形凸起的单链DNA或双链DNA结合而在溶液中形成。这些结果描绘了hnRNP A2/B1在抗病毒免疫和其他细胞过程中的潜在功能状态。
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