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New insights into the structural basis of DNA recognition by HINa and HINb domains of IFI16 Free
Xiangmin Ni1,2,†, Heng Ru2,†, Feng Ma3,†, Lixia Zhao2,†, Neil Shaw2, Yingang Feng4, Wei Ding2, Weibin Gong2, Qiaofeng Wang1, Songying Ouyang2,*, Genhong Cheng3,*, and Zhi-Jie Liu1,2,5,*
1Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, China
2National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
3Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA
4The Qingdao Engineering Laboratory of Single Cell Oil and Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China
5iHuman Institute, ShanghaiTech University, Shanghai 201210, China *Correspondence to:Zhi-Jie Liu, E-mail: zjliu@ibp.ac.cn; Genhong Cheng, E-mail: gcheng@mednet.ucla.edu; Songying Ouyang, E-mail: ouyangsy@moon.ibp.ac.cn
J Mol Cell Biol, Volume 8, Issue 1, February 2016, 51-61,  https://doi.org/10.1093/jmcb/mjv053
Keyword: interferon gamma-inducible protein 16 (IFI16), hematopoietic interferon-inducible nuclear (HIN) domain, DNA recognition, innate immune responses

Interferon gamma-inducible protein 16 (IFI16) senses DNA in the cytoplasm and the nucleus by using two tandem hematopoietic interferon-inducible nuclear (HIN) domains, HINa and HINb, through the cooperative assembly of IFI16 filaments on double-stranded DNA (dsDNA). The role of HINa in sensing DNA is not clearly understood. Here, we describe the crystal structure of the HINa domain in complex with DNA at 2.55 Å resolution and provide the first insight into the mode of DNA binding by the HINa domain. The structure reveals the presence of two oligosaccharide/nucleotide-binding (OB) folds with a unique DNA-binding surface. HINa uses loop L45 of the canonical OB2 fold to bind to the DNA backbone. The dsDNA is recognized as two single strands of DNA. Interestingly, deletion of HINb compromises the ability of IFI16 to induce IFN-β, while HINa mutants impaired in DNA binding enhance the production of IFN-β. These results shed light on the roles of IFI16 HIN domains in DNA recognition and innate immune responses.


Volume 8, Issue 1
February 2016