Structural Insight Into hnRNP A2/B1 Homodimerization and DNA Recognition.
Structural Insight Into hnRNP A2/B1 Homodimerization and DNA Recognition.
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DOI：
10.1016/j.jmb.2022.167920
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发表时间：
2022-12
影响因子：
5.6
通讯作者：
Yue-guang Liu;A. Abula;Haonan Xiao;Hangtian Guo;Tinghan Li;Le Zheng;Biqing Chen;Henry C. Nguyen;X. Ji
中科院分区：
文献类型：
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作者：
Yue-guang Liu;A. Abula;Haonan Xiao;Hangtian Guo;Tinghan Li;Le Zheng;Biqing Chen;Henry C. Nguyen;X. Ji
异质核核糖核蛋白A2/B1（hnRNPA 2/B1）是一种核DNA传感器。在病毒感染时，hnRNP A2/B1识别病原体来源的DNA作为同源二聚体，这是其易位到细胞质以激活干扰素应答的先决条件。然而，诱导hnRNPA 2/B1同源二聚化的DNA结合机制尚不清楚。在这里，我们显示了与U形ssDNA复合的hnRNP A2/B1的RNA识别基序（RRM）的晶体结构，其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，hnRNPA 2/B1同型二聚体的形式在溶液中结合到预先生成的ssDNA或dsDNA与U形凸起。这些结果描述了hnRNPA 2/B1在抗病毒免疫和其他细胞过程中的潜在功能状态。
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.