The ligand insertion hypothesis in the genomic action of steroid hormones

摘要: Gene regulation by steroids is tightly coupled to hormone concentration and stereochemistry. A key step binding of hormones receptors which interact with consensus DNA sequences known as response elements (HREs). The specificity strength do not correlate well hormonal activity suggesting an additional involving recognition ligand the gene. Stereospecific fit between base pairs correlation led proposal that such involves insertion into DNA. Here, feasibility was investigated using computer models glucocorticoid receptor domain bound its HRE. site reported accommodate glucocorticoids found in HRE exposed permit unwinding at this locus. resulting cavity unwound DNA/receptor interface cortisol remarkably well; formed hydrogen bonds both Current experimental evidence generally consistent domains undergoing a conformational change facilitates transfer interface. We propose rate limiting alterations receptor, or attenuate impair gene function.