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

Junji Iwahara, Mizuho Iwahara, Gary W. Daughdrill, Joseph Ford, Robert T. Clubb

Research output: Contribution to journalArticle

43 Citations (Scopus)

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 β-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.

Original languageEnglish (US)
Pages (from-to)1197-1209
Number of pages13
JournalEMBO Journal
Volume21
Issue number5
DOIs
StatePublished - Mar 1 2002
Externally publishedYes

Fingerprint

DNA
Transcription Factors
Helix-Turn-Helix Motifs
Amino Acids
Thymine
Adenine
Drosophila melanogaster
Immobilization
Serine
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance spectroscopy
Nucleotides

Keywords

  • ARID
  • AT-rich interaction domains
  • Dead ringer
  • DNA recognition
  • NMR
  • Structure

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

The structure of the Dead ringer-DNA complex reveals how AT-rich interaction domains (ARIDs) recognize DNA. / Iwahara, Junji; Iwahara, Mizuho; Daughdrill, Gary W.; Ford, Joseph; Clubb, Robert T.

In: EMBO Journal, Vol. 21, No. 5, 01.03.2002, p. 1197-1209.

Research output: Contribution to journalArticle

Iwahara, Junji ; Iwahara, Mizuho ; Daughdrill, Gary W. ; Ford, Joseph ; Clubb, Robert T. / The structure of the Dead ringer-DNA complex reveals how AT-rich interaction domains (ARIDs) recognize DNA. In: EMBO Journal. 2002 ; Vol. 21, No. 5. pp. 1197-1209.
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