Structural elements of an orphan nuclear receptor-DNA complex.
The nuclear hormone receptors form the largest known family of transcription factors. The current notion of receptor DNA discrimination, based solely on one major type of hexameric half-site and a highly conserved 66-residue core DNA-binding domain (DBD), does not adequately describe how more than 150 nonsteroid receptors differentiate among response elements. Here, we describe the 2.3 A crystal structure of the DNA-binding region of the orphan receptor RevErb arranged as a tandem homodimer on its optimal response element. The structure reveals the presence of a second major protein-DNA interface adjacent to the classical one involving the half-sites. A sequence comparison of orphan receptors suggests that unique minor-groove interactions involving the receptor hinge regions impart the necessary DNA and dimerization specificity.
Zhao
Q
Q
Department of Pharmacology, School of Medicine, University of Virginia, Charlottesville 22908, USA.
Khorasanizadeh
S
S
Miyoshi
Y
Y
Lazar
M A
MA
Rastinejad
F
F
D001665:Binding Sites / Q000502:physiology; D017124:Conserved Sequence; D003461:Crystallography; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D009690:Nucleic Acid Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D004268:DNA-Binding Proteins; C064353:NR1D1 protein, human; D009687:Nuclear Proteins; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D004247:DNA