Structural Insight Into hnRNP A2/B1 Homodimerization and DNA Recognition

Yue Liu; Abudureyimu Abula; Haonan Xiao; Hangtian Guo; Tinghan Li; Le Zheng; Biqing Chen; Henry C Nguyen; Xiaoyun Ji

doi:10.1016/j.jmb.2022.167920

Structural Insight Into hnRNP A2/B1 Homodimerization and DNA Recognition

J Mol Biol. 2023 Feb 1;435(3):167920. doi: 10.1016/j.jmb.2022.167920. Epub 2022 Dec 14.

Authors

Yue Liu¹, Abudureyimu Abula², Haonan Xiao¹, Hangtian Guo¹, Tinghan Li¹, Le Zheng¹, Biqing Chen³, Henry C Nguyen¹, Xiaoyun Ji⁴

Affiliations

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 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.
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 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; Engineering Research Center of Protein and Peptide Medicine, Ministry of Education, People's Republic of China. Electronic address: [email protected].

PMID: 36528084
DOI: 10.1016/j.jmb.2022.167920

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.

Keywords: RRMs domain; U-shaped DNA; crystal structure; hnRNP A2/B1; homodimerization.

MeSH terms

DNA / chemistry
Heterogeneous-Nuclear Ribonucleoprotein Group A-B* / chemistry
Heterogeneous-Nuclear Ribonucleoprotein Group A-B* / metabolism
Protein Multimerization*

Substances

DNA
Heterogeneous-Nuclear Ribonucleoprotein Group A-B
hnRNP A2