Glucocorticoid receptor sequence

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... 

The HREs of the steroid hormone receptors posses a palindromic structure, comparable to the DNA binding elements of procaryotic repressors (see fig. 4.7a). The glucocorticoid receptor, for example, binds as a homodimer to the two-fold symmetrical recognition sequence, whereby the receptor is already dimerized in solution. In complex with the DNA each subimit of the dimer contacts one half-site of the HRE. As a consequence of the two-fold repeat of the recognition sequence, a high affinity binding of the receptor dimer results (compare 1.2.4). 

Chandler, V. L., B. A. Maler, and K. R. Yamamoto, DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter responsive in vivo A steroid specific enhancer. Cell 33 489-499, 1983. 

The mineralocorticoid receptor (MR) mediates the sodium-retaining effects of aldosterone in the kidney, salivary glands, sweat glands, and colon. The human MR gene was cloned in 1987 and bears structural and functional kinships to the glucocorticoid receptor (11). It consists of 984 amino acids, spans 60 90 kb on chromosome 4q31.2 (50,51) and contains 10 exons including two exons (la and 1 p) that encode different 5 untranslated sequences whose expression is controlled by two different promoters (52). 

Fig. 3. DNA-binding finger structure proposed for TFIIIA [21] and steroid receptors. The amino acid sequence of the glucocorticoid receptor (GR) fingers are shown. Conserved amino acids in the receptors for progesterone (PR) and oestrogen (ER) are indicated by an asterisk, whereas differences are shown.

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