Structure of the heterodimeric ecdysone receptor DNA-binding complex.

Devarakonda S, Harp JM, Kim Y, Ozyhar A, Rastinejad F
EMBO J. 2003 22 (21): 5827-40

PMID: 14592980 · PMCID: PMC275426 · DOI:10.1093/emboj/cdg569

Ecdysteroids initiate molting and metamorphosis in insects via a heterodimeric receptor consisting of the ecdysone receptor (EcR) and ultraspiracle (USP). The EcR-USP heterodimer preferentially mediates transcription through highly degenerate pseudo-palindromic response elements, resembling inverted repeats of 5'-AGGTCA-3' separated by 1 bp (IR-1). The requirement for a heterodimeric arrangement of EcR-USP subunits to bind to a symmetric DNA is unusual within the nuclear receptor superfamily. We describe the 2.24 A structure of the EcR-USP DNA-binding domain (DBD) heterodimer bound to an idealized IR-1 element. EcR and USP use similar surfaces, and rely on the deformed minor groove of the DNA to establish protein-protein contacts. As retinoid X receptor (RXR) is the mammalian homolog of USP, we also solved the 2.60 A crystal structure of the EcR-RXR DBD heterodimer on IR-1 and found the dimerization and DNA-binding interfaces to be the same as in the EcR-USP complex. Sequence alignments indicate that the EcR-RXR heterodimer is an important model for understanding how the FXR-RXR heterodimer binds to IR-1 sites.

MeSH Terms (20)

Amino Acid Sequence Animals Base Sequence Binding Sites Dimerization DNA DNA-Binding Proteins Drosophila Drosophila Proteins Macromolecular Substances Models, Molecular Molecular Sequence Data Protein Structure, Quaternary Protein Structure, Tertiary Receptors, Cytoplasmic and Nuclear Receptors, Retinoic Acid Receptors, Steroid Retinoid X Receptors Static Electricity Transcription Factors

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