Mechanisms of DNA recognition by transcription factors

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An ongoing theme in our research has been to understand the structural basis for how diverse proteins recognize DNA in a sequence specific manner. This interest goes back to my post-doctoral work with Steve Harrison, where I determined the structure of the heterdimeric bZIP transcription factor, Fos-Jun or AP1, bound to DNA. In our lab, we have worked on the yeast meiotic regulator, Ndt80, showing that this protein is a member of the Ig-fold family of DNA binding proteins (with other members such as p53 and NF-κB). The high resolution of this structural work enabled us to define mechanisms of sequence specific recognition that are utilized by many other DNA binding proteins. These mechanisms include the recognition of 5’-pyrimidine-p-guanine-3’ steps by arginine residues that involve the unstacking of the DNA.

Figure 1.
Wong, J. J., Lu, J., Edwards, R. A., Frost, L. S., Glover, J. N. M. (2011) Structural basis of cooperative DNA recognition by the plasmid conjugation factor, TraM. Nucleic Acids Research Epub ahead of print
Lamoureux, J. S. and Glover, J. N. M. (2006) Principles of protein-DNA recognition revealed in the structural analysis of Ndt80-MSE DNA complexes. Structure 14(3):555-565. PDF
Lamoureux, J. S., Maynes, J. T. and Glover, J. N. M. (2004) Recognition of 5'-YpG-3' sequences by coupled stacking/hydrogen bonding interactions with amino acid residues. Journal Molecular Biology 335(2):399-408. PDF
Lamoureux, J. S., Stuart, D., Tsang, R., Wu, C. and Glover, J. N. M. (2002) Structure of the sporulation-specific transcription factor Ndt80 bound to DNA. The EMBO Journal 21:5721-5732. PDF
Tang, Y., Tie, F., Boros, I., Harrod, R., Glover, J. N. M., and Giam, C.-Z. (1998) An extended α-helix and specific amino acid residues opposite the DNA-binding surface of the cAMP response element binding protein basic domain are important for human T cell lymphotropic retrovirus Type I tax binding. The Journal of Biological Chemistry 273:27339-27346.
Chen, L., Glover, J. N. M., Hogan, P. G., Rao, A., and Harrison, S. C. (1998) Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA. Nature 392:42-48.
Glover, J. N. M. and Harrison, S. C. (1995) Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA. Nature 373:257-261.