A molecular code dictates sequence-specific DNA recognition by homeodomains

Giuseppe Damante, Lucia Pellizzari, Gennaro Esposito, Federico Fogolari, Paolo Viglino, Dora Fabbro, Gianluca Tell, Silvestro Formisano, Roberto Di Lauro

Research output: Contribution to journalArticlepeer-review


Most homeodomains bind to DNA sequences containing a 5'-CAAG-3' core motif, delineating a new mechanism for differential DIVA recognition by homeodomains. We investigated the molecular basis of the DNA binding specificity of TTF-1HD by both structural and functional approaches. As already suggested by the three-dimensional structure of TTF-1HD, the DNA binding specificities of the TTF-1. Antennapedia and Engrailed homeodomains, either wild-type or mutants, indicated that the amino acid residue in position 54 is involved in the recognition of the nucleotide at the 3' end of the core motif 5'NAAN-3'. The nucleotide at the 5' position of this core sequence is recognized by the amino acids located in position 6, 7 and 8 of the TTF-1 and Antennapedia homeodomains. These data, together with previous suggestions on the role of amino acids in position 50, indicate that the DNA binding specificity of homeodomains can be determined by a combinatorial molecular code. We also show that some specific combinations of the key amino acid residues involved in DNA recognition do not follow a simple, additive rule.

Original languageEnglish (US)
Pages (from-to)4992-5000
Number of pages9
JournalEMBO Journal
Issue number18
StatePublished - Sep 16 1996


  • DNA binding
  • DNA recognition
  • Homeodomain

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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