title: New insights into the structural basis of DNA recognition by HINa and HINb domains of IFI16.
abstract: 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.
authors.affiliation: Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, China National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Ni
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Ru
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Ma
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Zhao
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Neil
authors.initials: N
authors.lastname: Shaw
authors.affiliation: The 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.
authors.forename: Yingang
authors.initials: Y
authors.lastname: Feng
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Weibin
authors.initials: W
authors.lastname: Gong
authors.affiliation: Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, China.
authors.forename: Qiaofeng
authors.initials: Q
authors.lastname: Wang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China zjliu@ibp.ac.cn gcheng@mednet.ucla.edu ouyangsy@moon.ibp.ac.cn.
authors.forename: Songying
authors.initials: S
authors.lastname: Ouyang
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA zjliu@ibp.ac.cn gcheng@mednet.ucla.edu ouyangsy@moon.ibp.ac.cn.
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, China National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China iHuman Institute, ShanghaiTech University, Shanghai 201210, China zjliu@ibp.ac.cn gcheng@mednet.ucla.edu ouyangsy@moon.ibp.ac.cn.
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Liu
mesh_terms: D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains
chemical_list: D009687:Nuclear Proteins; D010750:Phosphoproteins; C076700:IFI16 protein, human; D004247:DNA
keywords: DNA recognition; hematopoietic interferon-inducible nuclear (HIN) domain; innate immune responses; interferon gamma-inducible protein 16 (IFI16)