Structure and Function of the Glucocorticoid Receptor DNA-Binding Domain
Steroids and other lipophilic hormones affect gene expression via specialized receptor proteins that reside in the cytoplasm or cell nucleus. Some features of this mechanism are illustrated by the well-characterized example of the glucocorticoid receptor: on binding the hormone, the receptor translocates from the cytoplasm to the nucleus, where it associates with particular sites in the genome and affects transcription rates of target genes. To date, some 30 distinct receptors sharing certain functional similarities with the glucocorticoid receptor have been identified. This closely related group has been termed the “steroid/nuclear receptor superfamily”, and members have been discovered in species as diverse as arthropods and mammals, representing some 500 million years of evolutionary divergence (Beato 1989; Parker 1991; Seagraves 1991; Laudet et al. 1992). The glucocorticoid receptor has been one of the more extensively studied members of the superfamily and has provided insight into the function of the steroid/nuclear receptors.
KeywordsRetinoic Acid Glucocorticoid Receptor Nuclear Receptor Major Groove Base Contact
Unable to display preview. Download preview PDF.
- Kim B, Little JW (1992) Dimerization of a specific DNA-binding protein on the DNA. Nature 255: 203–206Google Scholar
- Patel L, Abate C, Curran T (1990) Altered protein conformation on DNA binding by Fos and Jun. Nature 347:572–575Google Scholar
- Pavletich NP, Pabo CO (1991) Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A. Science 252: 809–817Google Scholar
- Perutz MF (1990) Mechanism of cooperativity and allosteric regulation in proteins. Cambridge University Press, CambridgeGoogle Scholar
- Rut AR, Hewison M, Kristjansson K, Luisi B, O’Riordan JLH, Hughes MR (1993) Mutations in the vitamin D receptor gene and their stereochemical consequences, (submitted)Google Scholar
- Sone T, Kerner SA, Saijo T, Takeda E, Pike JW (1991) Mutations in the DNA binding domain of the vitamin D receptor associated with hereditary resistance of 1,25- dihydroxyvitamin D3. In: Norman AW, Bouillon R, Thomasset M (eds) Vitamin D: gene regulation, structure-function analysis, and clinical applications. De Gruyter, New York, pp 84–85Google Scholar
- Towers T, Luisi BF, Asianov A, Freedman LP (1993) DNA target selectivity by the vitamin D3 receptor; Mechanism of dimer binding to an asymmetric repeat element. Proc Natl Acad Sci USA (in press)Google Scholar