The structure of the Dead ringer-DNA complex reveals how AT-rich interaction domains (ARIDs) recognize DNA

EMBO J. 2002 Mar 1;21(5):1197-209. doi: 10.1093/emboj/21.5.1197.

Abstract

The AT-rich interaction domain (ARID) is a DNA-binding module found in many eukaryotic transcription factors. Using NMR spectroscopy, we have determined the first ever three-dimensional structure of an ARID--DNA complex (mol. wt 25.7 kDa) formed by Dead ringer from Drosophila melanogaster. ARIDs recognize DNA through a novel mechanism involving major groove immobilization of a large loop that connects the helices of a non-canonical helix-turn-helix motif, and through a concomitant structural rearrangement that produces stabilizing contacts from a beta-hairpin. Dead ringer's preference for AT-rich DNA originates from three positions within the ARID fold that form energetically significant contacts to an adenine-thymine base step. Amino acids that dictate binding specificity are not highly conserved, suggesting that ARIDs will bind to a range of nucleotide sequences. Extended ARIDs, found in several sequence-specific transcription factors, are distinguished by the presence of a C-terminal helix that may increase their intrinsic affinity for DNA. The prevalence of serine amino acids at all specificity determining positions suggests that ARIDs within SWI/SNF-related complexes will interact with DNA non-sequence specifically.

Publication types

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

MeSH terms

  • Adenine / chemistry
  • Amino Acid Sequence
  • Animals
  • Base Pairing*
  • Binding Sites
  • Consensus Sequence
  • DNA / metabolism*
  • DNA-Binding Proteins / chemistry
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism*
  • Helix-Turn-Helix Motifs
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / metabolism*
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Serine / chemistry
  • Structure-Activity Relationship
  • Substrate Specificity
  • Thymidine / chemistry

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Homeodomain Proteins
  • Macromolecular Substances
  • Nuclear Proteins
  • Retn protein, Drosophila
  • Serine
  • DNA
  • Adenine
  • Thymidine

Associated data

  • PDB/1KQQ