Structural Insight Into hnRNP A2/B1 Homodimerization and DNA Recognition

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 crys-tal 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 mutagen-esis 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.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://crea-tivecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) functions as a nuclear DNA sensor and is involved in antiviral immunity. The crystal structure of its RNA recognition motif (RRM) complexed with U-shaped single-stranded DNA (ssDNA) reveals a new protein dimer formation. Biochemical assays and mutagenesis studies confirm that hnRNP A2/B1 homodimerizes in solution by binding to ssDNA or double-stranded DNA (dsDNA) with a U-shaped bulge.