title: Relationship of structure and function of DNA-binding domain in vitamin D receptor.
abstract: While the structure of the DNA-binding domain (DBD) of the vitamin D receptor (VDR) has been determined in great detail, the roles of its domains and how to bind the motif of its target genes are still under debate. The VDR DBD consists of two zinc finger modules and a C-terminal extension (CTE), at the end of the C-terminal of each structure presenting α-helix. For the first zinc finger structure, N37 and S-box take part in forming a dimer with 9-cis retinoid X receptor (RXR), while V26, R50, P-box and S-box participate in binding with VDR response elements (VDRE). For the second zinc finger structure, P61, F62 and H75 are essential in the structure of the VDR homodimer with the residues N37, E92 and F93 of the downstream of partner VDR, which form the inter-DBD interface. T-box of the CTE, especially the F93 and I94, plays a critical role in heterodimerization and heterodimers-VDRE binding. Six essential residues (R102, K103, M106, I107, K109, and R110) of the CTE α-helix of VDR construct one interaction face, which packs against the DBD core of the adjacent symmetry mate. In 1,25(OH)2D3-activated signaling, the VDR-RXR heterodimer may bind to DR3-type VDRE and ER9-type VDREs of its target gene directly resulting in transactivation and also bind to DR3-liked nVDRE of its target gene directly resulting in transrepression. Except for this, 1α,25(OH)2D3 ligand VDR-RXR may bind to 1αnVDRE indirectly through VDIR, resulting in transrepression of the target gene. Upon binding of 1α,25(OH)2D3, VDR can transactivate and transrepress its target genes depending on the DNA motif that DBD binds.
authors.affiliation: Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang 443002, China. wanlinyan0224@163.com.
authors.forename: Lin-Yan
authors.initials: LY
authors.lastname: Wan
authors.affiliation: Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang 443002, China. zhangyanqiong@ctgu.edu.cn.|Department of Pathogenic Biology and Immunology, Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang 443002, China. zhangyanqiong@ctgu.edu.cn.
authors.forename: Yan-Qiong
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang 443002, China. 15572753727@163.com.
authors.forename: Meng-Di
authors.initials: MD
authors.lastname: Chen
authors.affiliation: Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang 443002, China. cbliu@ctgu.edu.cn.|Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang 443002, China. cbliu@ctgu.edu.cn.
authors.forename: Chang-Bai
authors.initials: CB
authors.lastname: Liu
authors.affiliation: Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang 443002, China. wujiangfeng@ctgu.edu.cn.|Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang 443002, China. wujiangfeng@ctgu.edu.cn.
authors.forename: Jiang-Feng
authors.initials: JF
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D018167:Receptors, Calcitriol / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D018167:Receptors, Calcitriol; D004247:DNA
keywords: CTE; VDR DBD; VDRE; nVDRE; zinc finger structure