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 journalArticle

Abstract

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
Volume15
Issue number18
StatePublished - Sep 16 1996

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Amino Acids
DNA
Nucleotides
DNA sequences

Keywords

  • DNA binding
  • DNA recognition
  • Homeodomain

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Damante, G., Pellizzari, L., Esposito, G., Fogolari, F., Viglino, P., Fabbro, D., ... Di Lauro, R. (1996). A molecular code dictates sequence-specific DNA recognition by homeodomains. EMBO Journal, 15(18), 4992-5000.

A molecular code dictates sequence-specific DNA recognition by homeodomains. / Damante, Giuseppe; Pellizzari, Lucia; Esposito, Gennaro; Fogolari, Federico; Viglino, Paolo; Fabbro, Dora; Tell, Gianluca; Formisano, Silvestro; Di Lauro, Roberto.

In: EMBO Journal, Vol. 15, No. 18, 16.09.1996, p. 4992-5000.

Research output: Contribution to journalArticle

Damante, G, Pellizzari, L, Esposito, G, Fogolari, F, Viglino, P, Fabbro, D, Tell, G, Formisano, S & Di Lauro, R 1996, 'A molecular code dictates sequence-specific DNA recognition by homeodomains', EMBO Journal, vol. 15, no. 18, pp. 4992-5000.
Damante G, Pellizzari L, Esposito G, Fogolari F, Viglino P, Fabbro D et al. A molecular code dictates sequence-specific DNA recognition by homeodomains. EMBO Journal. 1996 Sep 16;15(18):4992-5000.
Damante, Giuseppe ; Pellizzari, Lucia ; Esposito, Gennaro ; Fogolari, Federico ; Viglino, Paolo ; Fabbro, Dora ; Tell, Gianluca ; Formisano, Silvestro ; Di Lauro, Roberto. / A molecular code dictates sequence-specific DNA recognition by homeodomains. In: EMBO Journal. 1996 ; Vol. 15, No. 18. pp. 4992-5000.
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