A novel, highly conserved structural motif is present in all members of the steroid receptor superfamily.
Steroid and thyroid hormone receptor superfamily members are ligand potentiated transcription factors. Recent evidence indicates that one aspect of steroid receptor action is an interaction with other trans-acting factors, such as the glucocorticoid receptor with the AP1 transcription factor, for example. Using a structural approach to identify domains of the glucocorticoid receptor responsible for interactions with affiliated transacting factors and DNA, we have identified a putative helix-turn-zipper motif that is conserved in all steroid, thyroid hormone, retinoic acid, and vitamin-D3 receptors. This structural motif is also conserved among new members of the family, the peroxisome proliferator-activated receptors and the retinoid-X receptors. This structural domain is characterized by a pair of amino acids (I,L,V)P that is conserved in all superfamily members. Additional characteristics include six heptad repeats of hydrophobic amino acids, four of which form a canonical leucine zipper in the rat glucocorticoid receptor. Although this leucine repeat is not absolutely conserved among superfamily members, the periodicity of hydrophobic residues is conserved throughout. Based on sequence analyses from the GenEMBL and SwissProt databases using the Genetics Computer Group and MacVector sequence analysis software packages, and the Brookhaven structural database, we present evidence for a novel structural domain, a helix-turn-zipper that is conserved in all superfamily members, and may function in transactivation of cognate genes.
Maksymowych
A B
AB
Department of Pharmacology, Thomas Jefferson University, Philadelphia, PA 19107.
Hsu
T C
TC
Litwack
G
G
D000595:Amino Acid Sequence; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011965:Receptors, Glucocorticoid / Q000737:chemistry* / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000737:chemistry* / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D012984:Software; D014158:Transcription, Genetic
D011965:Receptors, Glucocorticoid; D011988:Receptors, Thyroid Hormone