Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
Get into shape: new insights into the broadly observed mechanism of DNA shape readout and its relation to genetic variation
Various biological processes are driven by interactions between proteins and their DNA binding sites. To achieve DNA binding specificity, an interplay between base and shape readout modes by proteins is important (Rohs et al., 2010). Recently, we have demonstrated the important role of DNA shape readout for different transcription factors and other protein families (Rohs et al., 2009). This mechanism includes the recognition of structural features of the DNA and electrostatic interactions between the narrow DNA minor groove and arginine residues. Here, we expand this finding and demonstrate how histidine residues can play a similar role in DNA shape readout, and illustrate that shape readout regulates many other protein-DNA interactions beyond transcription. Whereas we have previously demonstrated the importance of shape readout for the homeodomain family of transcription factors (Slattery et al., 2011), we now show the broader spectrum of this mechanism for protein families involved in DNA looping, origin recognition, and transcription initiation. In a related approach, we study the effect that single nucleotide variants can have on DNA shape readout. These findings broadly expand our current understanding of the mechanisms by which proteins can recognize DNA, and raise many interesting questions as to how genetic variations in non-coding regions of the genome affect protein-DNA binding.
R. Rohs, S.M. West, A. Sosinsky, P. Liu, R.S. Mann, B. Honig, 2009. The role of DNA shape in protein–DNA recognition. Nature 461, 1248–1253.
M. Slattery, T. Riley, P. Liu, N. Abe, P. Gomez-Alcala, I. Dror, T. Zhou, R. Rohs, B. Honig, H.J. Bussemaker, R.S. Mann,, 2011. Cofactor Binding Evokes Latent Differences in DNA Binding Specificity between Hox Proteins. Cell 147, 1270–1282.
Ana C. D. Machado
Molecular and Computational Biology Program