Some recent works on Protein-DNA interactions.

Specific protein-DNA binding has been thought, so far, to be a two-step process. However, a recent study by Sanchez et al (PNAS, 107:7751-7756. April 27, 2010) show that it may not be always the case. They find an equally probable second route – a route that has more rougher energy landscape. By a series of systematic mutations in the protein, the characterize the energy landscape of the second route – which again involves atleast two intermediates. The overall picture is that, there is an initial transition state ensemble with non-native contacts that drive the system into a kinetic trap. These non-native contacts are slowly rearranged into native-like interactions.
There are two points that are quite interesting:

1. That the second route is significantly probable.
2. To think of additional factors such as DNA bending in such a rough energy landscape is mind boggling!

While this study delineates the pathways to protein –DNA binding, yet another study (Genes and Development, 24:814-826) shows that the *shape* of the DNA minor groove directs binding by the protein FIS, a DNA-bending protein. The results of the study seem to suggest that FIS initially selects DNA targets with *intrinsically* narrow minor grooves and then it compresses the minor groove and bends the DNA. The study re-iterates the idea that the shape of the DNA is more important than its sequence – atleast in the noncoding regions, as shown by an earlier study (Science, Vol 324, 389-392, 2009).

Even as it is becoming clearer that the shape of the DNA is important, I think there is a long way to go in understanding what changes occur in the intrinsic properties of the DNA/protein that eventually modulate the structure.