Structure of the Even-skipped homeodomain complexed to AT-rich DNA: New perspectives on homeodomain specificity

Joel A. Hirsch, Aneel K. Aggarwal

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Even-skipped is a homeobox gene important in controlling segment patterning in the embryonic fruit fly. Its homeobox encodes a DNA binding domain which binds with similar affinities to two DNA consensus sequences, one AT-rich, the other GC-rich. We describe a crystallographic analysis of the Even-skipped homeodomain complexed to an AT-rich oligonucleotide at 2.0 Å resolution. The structure reveals a novel arrangement of two homeodomains bound to one 10 bp DNA sequence in a tandem fashion. This arrangement suggests a mechanism for the homeoproteins' regulatory specificity. In addition, the functionally important residue Gln50 is observed in multiple conformations making direct and water-mediated hydrogen bonds with the DNA bases.

Original languageEnglish
Pages (from-to)6280-6291
Number of pages12
JournalEMBO Journal
Volume14
Issue number24
DOIs
StatePublished - 1995
Externally publishedYes

Keywords

  • Crystal structure
  • Even-skipped
  • Homeodomain
  • Protein-DNA interactions

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