Structure of the retinoid X receptor alpha DNA binding domain: a helix required for homodimeric DNA binding.
The three-dimensional solution structure of the DNA binding domain (DBD) of the retinoid X receptor alpha (RXR alpha) was determined by nuclear magnetic resonance spectroscopy. The two zinc fingers of the RXR DBD fold to form a single structural domain that consists of two perpendicularly oriented helices and that resembles the corresponding regions of the glucocorticoid and estrogen receptors (GR and ER, respectively). However, in contrast to the DBDs of the GR and ER, the RXR DBD contains an additional helix immediately after the second zinc finger. This third helix mediates both protein-protein and protein-DNA interactions required for cooperative, dimeric binding of the RXR DBD to DNA. Identification of the third helix in the RXR DBD thus defines a structural feature required for selective dimerization of the RXR on hormone response elements composed of half-sites (5'-AGGTCA-3') arranged as tandem repeats.
Lee
M S
MS
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
Kliewer
S A
SA
Provencal
J
J
Wright
P E
PE
Evans
R M
RM
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D018168:Receptors, Retinoic Acid; D012091:Repetitive Sequences, Nucleic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D004247:DNA