Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
Covariation between homeodomains and the DNA shape of their binding sites provides new insights into protein-DNA recognition
It is well established that transcription factors (TFs) identify their binding sites through direct contacts with unique chemical groups of the base pairs mainly in the major groove. A second type of mechanism, which has been relatively less studied, is the readout of DNA shape, in which the protein recognizes the three-dimensional DNA structure (Rohs et al., 2010). Here we focused on the homeodomain family of TFs and analyzed the DNA shape of thousands of sequences in order to study the correlation between the amino acid sequence of homeodomains and the nucleotide sequence and shape of their DNA binding sites. We have found regions in the homeodomains that are significantly correlated with the sequence or with the shape of their preferred binding sites, demonstrating the role of the different homeodomain regions in attaining binding specificity through the different modes of recognition. Next, we predicted specific residues in homeodomains which likely play an important role in DNA recognition through DNA shape attributes. Furthermore, we show that adding DNA shape information to the characterization of TF binding sites can improve predictions of homeodomain binding specificity. Finally, our work indicates that DNA shape information can provide new mechanistic insights into TF binding.
Rohs R, Jin X, West SM, Joshi R, Honig B, Mann RS.(2010). Origins of specificity in protein-DNA recognition. Annu Rev Biochem 79:233–269.
1Molecular and Computational Biology Program