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

    Fingerprint

    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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