Structure of the heterodimeric ecdysone receptor DNA-binding complex

EMBO J. 2003 Nov 3;22(21):5827-40. doi: 10.1093/emboj/cdg569.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Macromolecular Substances
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Receptors, Steroid
  • Retinoid X Receptors
  • Transcription Factors
  • USP protein, Drosophila
  • ecdysone receptor
  • DNA