Vitamin D receptor mutant H305F (VDR H305F)

The Vitamin D receptor (VDR) is a ligand-activated nuclear receptor that mediates the biological effects of vitamin D by regulating the transcription of numerous target genes (UniProt P11473). It is primarily activated by 1,25-dihydroxyvitamin D3 (calcitriol), which triggers the receptor's heterodimerization with the retinoid X receptor (RXR) and subsequent binding to vitamin D response elements (VDREs) in the promoter regions of target genes. The H305F mutation represents a substitution of histidine at position 305 with phenylalanine within the ligand-binding domain (LBD). This specific residue, H305, is critical for forming a hydrogen bond with the 1-alpha-hydroxyl group of calcitriol, and its mutation to phenylalanine—a non-polar, bulky residue—is often used in structural biology to study the stabilization of the active conformation and the specificity of ligand docking (Rochel et al., 2000, PubMed: 11162433). VDR plays a central role in maintaining mineral homeostasis, particularly calcium and phosphorus levels, and is vital for bone mineralization and immune system modulation. Clinically, VDR is a major therapeutic target for conditions such as osteoporosis, secondary hyperparathyroidism, and psoriasis. The H305F mutant serves as a significant research model for understanding how modifications in the binding pocket affect the efficacy and potency of vitamin D analogs (Yamada et al., 2002, PubMed: 12145333).

Other names

NR1I1 H305F1,25-dihydroxyvitamin D3 receptor mutant H305FNuclear receptor subfamily 1 group I member 1 mutant H305F

Ligand-activated transcription factor that heterodimerizes with the Retinoid X Receptor (RXR) to bind Vitamin D Response Elements (VDREs) and regulate gene expression.