This entry represents the DNA-binding domain of vitamin D receptors (VDR). It is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. VDR interacts with a VDR response element, a direct repeat of GGTTCA DNA site with 3 bp spacer upstream of the target gene, and modulates the rate of transcriptional initiation []. VDR is a member of the nuclear receptor (NR) superfamily that functions as classical endocrine receptors. VDR controls a wide range of biological activities including calcium metabolism, cell proliferation and differentiation, and immunomodulation. VDR is a high-affinity receptor for the biologically most active Vitamin D metabolite, 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) []. The binding of the ligand to the receptor induces a conformational change of the ligand binding domain (LBD) with consequent dissociation of corepressors. Upon ligand binding, VDR forms a heterodimer with the retinoid X receptor (RXR) that binds to vitamin D response elements (VDREs), recruits coactivators. This leads to the expression of a large number of genes. Approximately 200 human genes are considered to be primary targets of VDR and even more genes are regulated indirectly []. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, VDR has a central well conserved DNA binding domain (DBD) [], a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD) [, ].
Steroid or nuclear hormone receptors (NRs) constitute an important super-family of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, celldifferentiation and homeostasis. Members of the superfamily include thesteroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [, ]. In addition to C-terminalligand-binding domains, these nuclear receptors contain a highly-conserved,N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand,steroid hormone receptors are thought to be weakly associated with nuclearcomponents; hormone binding greatly increases receptor affinity.NRs are extremely important in medical research, a large number of thembeing implicated in diseases such as cancer, diabetes, hormone resistancesyndromes, etc. While several NRs act as ligand-inducible transcriptionfactors, many do not yet have a defined ligand and are accordingly termed "orphan"receptors. During the last decade, more than 300 NRs have beendescribed, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.The vitamin D receptor (VDR) mediates the signal of 1-a,25-dihydroxyvitamin D3 by binding to vitamin D responsive elements - it functions either as a homodimer, or as a heterodimer of vitamin D and retinoid X receptorsubunits. Deficiency of VDR causes type IIA rickets [].
