Key result
The crystal structure of the hnRNP A2/B1 RNA recognition motif in complex with U-shaped ssDNA reveals the mechanism of its homodimerization, a prerequisite for antiviral immune response activation.
Why the study?
Heterogeneous nuclear ribonucleoprotein A2/B1 recognizes pathogen-derived DNA as a homodimer to activate the interferon response, but the DNA binding mechanism inducing homodimerization is unknown.
This study provides structural insights into how hnRNP A2/B1 homodimerizes upon binding to U-shaped DNA, which is relevant for its role in antiviral immunity.
Structural insights into hnRNP A2/B1 may guide antiviral research; leaves open translation from animal models.
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.
No takes yet. Share an insight, caveat, or question.
Liu et al. (2022) studied this question. The crystal structure of the hnRNP A2/B1 RNA recognition motif in complex with U-shaped ssDNA reveals the mechanism of its homodimerization, a prerequisite for antiviral immune response activation.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: