Structural determinants of nuclear receptor assembly on DNA direct repeats.
Nuclear receptor heterodimers recognize response elements composed of two direct repeats of the consensus sequence 5'-AGGTCA-3' separated by one to five base pairs. The 1.9 A crystal structure of the complex formed by the DNA-binding domains of the 9-cis retinoic acid receptor and thyroid hormone receptor bound to a thyroid-response element shows that the subunits interact through a DNA-supported interface involving the carboxy-terminal extension of the DNA-binding domain of the thyroid hormone receptor. The stereochemistry suggests a mechanism by which heterodimers recognize the inter-half-site spacing between direct repeats.
Rastinejad
F
F
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06510, USA.
Perlmann
T
T
Evans
R M
RM
Sigler
P B
PB
D000595:Amino Acid Sequence; D001483:Base Sequence; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018168:Receptors, Retinoic Acid / Q000737:chemistry* / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000737:chemistry* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D004268:DNA-Binding Proteins; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D004247:DNA