The domain structure and iron coordination of the Rieske domain is very similar to that of the cytochrome bc1 domain. The active-site iron center of one of the alpha subunits is directly connected by hydrogen bonds through a single amino acid, Asp205, to the Rieske [2Fe-2S] center in a neighboring alpha subunit. This is likely to be the main route for electron transfer.

Here we describe the three-dimensional crystal structures of human glucocorticoid receptor ligand-binding domain (GR-LBD) in complex with the antagonist RU-486 at 2.3 Å resolution and with the agonist dexamethasone ligand together with a coactivator peptide at 2.8 Å. The RU-486 structure was solved in several different crystal forms, two with helix 12 intact (GR1 and GR3) and one with a protease-digested C terminus (GR2). In GR1, part of helix 12 is in a position that covers the co-activator pocket, whereas in the GR3, domain swapping is seen between the crystallographically identical subunits in the GR dimer. An arm consisting of the end of helix 11 and beyond stretches out from one molecule, and helix 12 binds to the other LBD, partly blocking the coactivator pocket of that molecule. This type of GR-LBD dimer has not been described before but might be an artifact from crystallization. Furthermore, the subunits of the GR3 dimers are covalently connected via a disulfide bond between the Cys-736 residues in the two molecules. All three RU-486 GR-LBD structures show that GR has a very flexible region between the end of helix 11 and the end of helix 12.The glucocorticoid receptor (GR) 1 is a foundational member of the nuclear receptor family. A large part of the basic knowledge of the mechanism of nuclear receptor function and action has been obtained by analysis of glucocorticoid receptor function. The three-domain structure of the nuclear receptor was originally described based on results from proteolytic cleavage of GR (1, 2). The first specific binding of a nuclear receptor to a defined DNA sequence, the glucocorticoid response element, was shown using purified GR (3, 4), and GR was the first steroid receptor to be cloned (partial clone) (5). The first threedimensional structure of a nuclear receptor was obtained when the structure of the GR DNA-binding domain was solved (6, 7). However, until recently, the structure of the GR ligand-binding domain (LBD) has proven elusive. The structures of numerous other nuclear receptor LBDs have been described, including those of most of the homologues of progesterone and androgen receptors (8, 9). Very recently, the first GR-LBD structure was described in complex with the agonist dexamethasone and a coactivator peptide (10).The four steroid receptors, GR, the progesterone (PR), androgen (AR), and mineralocorticoid receptors, are very closely related. They all bind to response elements with the same degenerate consensus sequence (11), and there is considerable overlap in ligand specificity and action (12)(13)(14). Progesterone is a glucocorticoid antagonist, and many synthetic progestins are also androgens. Glucocorticoids, and particularly the endogenous hormone cortisol, bind with similar affinities to both GR and the mineralocorticoid receptor, although aldosterone is a poor GR agonist. Thus, detailed structural and functional data will be needed to understand the specific function of these four steroid receptors. Despite the problems purifying and crystallizing GR-LBD...

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