A molecular code dictates sequence-specific DNA recognition by homeodomains - PubMed (original) (raw)

. 1996 Sep 16;15(18):4992-5000.

Affiliations

• PMID: 8890172
• PMCID: PMC452237

A molecular code dictates sequence-specific DNA recognition by homeodomains

G Damante et al. EMBO J. 1996.

Abstract

Most homeodomains bind to DNA sequences containing the motif 5'-TAAT-3'. The homeodomain of thyroid transcription factor 1 (TTF-1HD) binds to sequences containing a 5'-CAAG-3' core motif, delineating a new mechanism for differential DNA 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.

PubMed Disclaimer

Similar articles

• Sequence-specific DNA recognition by the thyroid transcription factor-1 homeodomain.
  Damante G, Fabbro D, Pellizzari L, Civitareale D, Guazzi S, Polycarpou-Schwartz M, Cauci S, Quadrifoglio F, Formisano S, Di Lauro R. Damante G, et al. Nucleic Acids Res. 1994 Aug 11;22(15):3075-83. doi: 10.1093/nar/22.15.3075. Nucleic Acids Res. 1994. PMID: 7915030 Free PMC article.
• In the TTF-1 homeodomain the contribution of several amino acids to DNA recognition depends on the bound sequence.
  Fabbro D, Tell G, Leonardi A, Pellizzari L, Pucillo C, Lonigro R, Formisano S, Damante G. Fabbro D, et al. Nucleic Acids Res. 1996 Sep 1;24(17):3283-8. doi: 10.1093/nar/24.17.3283. Nucleic Acids Res. 1996. PMID: 8811078 Free PMC article.
• Comparative stability analysis of the thyroid transcription factor 1 and Antennapedia homeodomains: evidence for residue 54 in controlling the structural stability of the recognition helix.
  Tell G, Acquaviva R, Formisano S, Fogolari F, Pucillo C, Damante G. Tell G, et al. Int J Biochem Cell Biol. 1999 Nov;31(11):1339-53. doi: 10.1016/s1357-2725(99)00047-3. Int J Biochem Cell Biol. 1999. PMID: 10605826
• Getting hydrophilic compounds into cells: lessons from homeopeptides.
  Prochiantz A. Prochiantz A. Curr Opin Neurobiol. 1996 Oct;6(5):629-34. doi: 10.1016/s0959-4388(96)80095-x. Curr Opin Neurobiol. 1996. PMID: 8937827 Review.
• [Structural aspects of homeodomain interactions with DNA].
  Ledneva RK, Alekseevskiĭ AV, Vasil'ev SA, Spirin SA, Kariagina AS. Ledneva RK, et al. Mol Biol (Mosk). 2001 Sep-Oct;35(5):764-77. Mol Biol (Mosk). 2001. PMID: 11605528 Review. Russian.

Cited by

• Analysis of homeodomain specificities allows the family-wide prediction of preferred recognition sites.
  Noyes MB, Christensen RG, Wakabayashi A, Stormo GD, Brodsky MH, Wolfe SA. Noyes MB, et al. Cell. 2008 Jun 27;133(7):1277-89. doi: 10.1016/j.cell.2008.05.023. Cell. 2008. PMID: 18585360 Free PMC article.
• Context-dependent DNA recognition code for C2H2 zinc-finger transcription factors.
  Liu J, Stormo GD. Liu J, et al. Bioinformatics. 2008 Sep 1;24(17):1850-7. doi: 10.1093/bioinformatics/btn331. Epub 2008 Jun 27. Bioinformatics. 2008. PMID: 18586699 Free PMC article.
• Predicting the binding preference of transcription factors to individual DNA k-mers.
  Alleyne TM, Peña-Castillo L, Badis G, Talukder S, Berger MF, Gehrke AR, Philippakis AA, Bulyk ML, Morris QD, Hughes TR. Alleyne TM, et al. Bioinformatics. 2009 Apr 15;25(8):1012-8. doi: 10.1093/bioinformatics/btn645. Epub 2008 Dec 16. Bioinformatics. 2009. PMID: 19088121 Free PMC article.
• Hydrogen-deuterium exchange studies of the rat thyroid transcription factor 1 homeodomain.
  Esposito G, Fogolari F, Damante G, Formisano S, Tell G, Leonardi A, Di Lauro R, Viglino P. Esposito G, et al. J Biomol NMR. 1997 Jun;9(4):397-407. doi: 10.1023/a:1018350611521. J Biomol NMR. 1997. PMID: 9255944
• Thyroid transcription factor 1, a homeodomain containing transcription factor, contributes to regulating periodic oscillations in GnRH gene expression.
  Matagne V, Kim JG, Ryu BJ, Hur MK, Kim MS, Kim K, Park BS, Damante G, Smiley G, Lee BJ, Ojeda SR. Matagne V, et al. J Neuroendocrinol. 2012 Jun;24(6):916-29. doi: 10.1111/j.1365-2826.2012.02302.x. J Neuroendocrinol. 2012. PMID: 22356123 Free PMC article.

References

1. 1. Mol Cell Biol. 1994 Aug;14(8):5066-75 - PubMed
2. 1. Cell. 1994 Jul 29;78(2):211-23 - PubMed
3. 1. Biochemistry. 1994 Aug 9;33(31):9187-94 - PubMed
4. 1. EMBO J. 1994 Aug 1;13(15):3551-60 - PubMed
5. 1. Nucleic Acids Res. 1994 Aug 11;22(15):3075-83 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Europe PubMed Central
  • PubMed Central
  • Wiley

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • FlyBase

• Research Materials

  • NCI CPTC Antibody Characterization Program