Glucocorticoid interactions

Figure 10.11 Sequence-specific interactions between DNA (yellow) and the recognition helix (red) of the glucocorticoid receptor. Three residues, Lys 461, Val 462 and Arg 466 make specific contacts with the edges of the bases In the major groove.

The individual domains of the two receptors both have structures similar to that of the glucocorticoid receptor, and they bind to DNA in a similar way, with their recognition helices in the major groove. The dimer contacts are, however, totally different. In the glucocorticoid receptor, which binds to a palindromic DNA sequence like the 434 repressor described in Chapter 8, the domains interact symmetrically in a head-to-head fashion equivalent... 

Luisi, B.F., et al. Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. 

Multiple drug interactions may occur with the glucocorticoids. Table 50-2 identifies select clinically significant interactions. 

Ligand-bound corticosteroid receptors have been shown to interact to form heterodimers with other transcription factors, such as the jun protein. Such interactions are responsible for transactivation of the ds-regulatory sites known as AP-1 sites and for the glucocorticoid-mediated suppression of transcription, such as that seen in the pro-opiomelanocortin gene. A number of such specific protein interactions have been reported these interactions and their locations relative to other transcription factors transform a ubiquitous steroid hormone signal into a tissue-specific, graded cellular response. 

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