Structural Insight Into hnRNP A2/B1 Homodimerization and DNA Recognition |
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| Affiliation: | 1. 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;2. School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, Xinjiang 830054, People’s Republic of China;3. Research Center of Chinese Medicine/Central Laboratory, Jiangsu Province Hospital of Chinese Medicine/ the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, People’s Republic of China;4. Engineering Research Center of Protein and Peptide Medicine, Ministry of Education, People’s Republic of China |
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| Abstract: | 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. |
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| Keywords: | hnRNP A2/B1 RRMs domain crystal structure homodimerization U-shaped DNA hnRNP A2/B1" },{" #name" :" keyword" ," $" :{" id" :" pc_o0T2XliauP" }," $$" :[{" #name" :" text" ," _" :" heterogeneous nuclear ribonucleoprotein A2/B1 RRM" },{" #name" :" keyword" ," $" :{" id" :" pc_8jGBNoIfP9" }," $$" :[{" #name" :" text" ," _" :" RNA recognition motif PrLD" },{" #name" :" keyword" ," $" :{" id" :" pc_YmmVbDPRUV" }," $$" :[{" #name" :" text" ," _" :" prion-like domain NLS" },{" #name" :" keyword" ," $" :{" id" :" pc_Nmjh8hsCgd" }," $$" :[{" #name" :" text" ," _" :" nuclear localization signal NAs" },{" #name" :" keyword" ," $" :{" id" :" pc_1ctJRsxcMk" }," $$" :[{" #name" :" text" ," _" :" nucleic acids PRRs" },{" #name" :" keyword" ," $" :{" id" :" pc_b7GUvWfG8j" }," $$" :[{" #name" :" text" ," _" :" pattern recognition receptors cGAS" },{" #name" :" keyword" ," $" :{" id" :" pc_wSdov3JiSW" }," $$" :[{" #name" :" text" ," _" :" cyclic GMP-AMP synthase IFI16" },{" #name" :" keyword" ," $" :{" id" :" pc_ywAyi2noMZ" }," $$" :[{" #name" :" text" ," _" :" interferon gamma-inducible protein 16 JMJD6" },{" #name" :" keyword" ," $" :{" id" :" pc_MT2MKT6ocv" }," $$" :[{" #name" :" text" ," _" :" jumonji domain-containing 6 protein TRS" },{" #name" :" keyword" ," $" :{" id" :" pc_QjEkgoWDF7" }," $$" :[{" #name" :" text" ," _" :" telomeric repeat sequence G4" },{" #name" :" keyword" ," $" :{" id" :" pc_ok5GpjaV42" }," $$" :[{" #name" :" text" ," _" :" G-quadruplex PQS" },{" #name" :" keyword" ," $" :{" id" :" pc_FfxE8FSJIe" }," $$" :[{" #name" :" text" ," _" :" potential quadruplex-forming sequences HSV" },{" #name" :" keyword" ," $" :{" id" :" pc_m7j20VsnMm" }," $$" :[{" #name" :" text" ," _" :" herpesvirus HAdV" },{" #name" :" keyword" ," $" :{" id" :" pc_zpPtPcbRSd" }," $$" :[{" #name" :" text" ," _" :" human adenovirus A2REcs" },{" #name" :" keyword" ," $" :{" id" :" pc_2fcEgoJwC5" }," $$" :[{" #name" :" text" ," _" :" hnRNP A2 response element cis-acting sequence EMSA" },{" #name" :" keyword" ," $" :{" id" :" pc_FRNuT185Y8" }," $$" :[{" #name" :" text" ," _" :" electrophoretic mobility shift assay ITC" },{" #name" :" keyword" ," $" :{" id" :" pc_4l1vFMQg8j" }," $$" :[{" #name" :" text" ," _" :" isothermal titration calorimetry assay AUC" },{" #name" :" keyword" ," $" :{" id" :" pc_YOixT64BvT" }," $$" :[{" #name" :" text" ," _" :" analytical ultracentrifugation TUS-ssDNA" },{" #name" :" keyword" ," $" :{" id" :" pc_DqqQF8M7ea" }," $$" :[{" #name" :" text" ," _" :" U-shaped TRS-ssDNA CD" },{" #name" :" keyword" ," $" :{" id" :" pc_iyzkT4zQaR" }," $$" :[{" #name" :" text" ," _" :" circular dichroism spectroscopy SEC" },{" #name" :" keyword" ," $" :{" id" :" pc_suDBsYj4OB" }," $$" :[{" #name" :" text" ," _" :" size exclusion chromatography |
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