2009 News

Minor Groove Insertion of Scr Residues His−12 and Arg3 in fkh250

Minor Groove Insertion of Scr Residues His−12 and Arg3 in fkh250. (A) Electron densities for Arg3 and His−12 in the fkh250 complex. (B) Details of the His−12–Arg3 interaction and water-mediated interactions with Thy14, Thy29, and Thy30 of fkh250

Although the basic structure of the double helix has been known since the classic work of Watson and Crick. it has become increasingly clear that the helix is not regular and that its shape depends on nucleotide sequence. In two recent papers in Cell and Nature, Barry Honig, Richard Mann and their colleagues in C2B2 and the Department of Biochemistry and Molecular Biophysics have shown that sequence-dependent variations in the helix shape allow DNA-binding proteins to recognize their specific binding sites.

This discovery was based initially on studies of Hox proteins that play a role in determining the anterior/posterior axis of embryos. Different Hox proteins must bind their various DNA targets with high specificity, and it was unclear how this was achieved. The researchers found that Hox proteins were able to recognize the width of the minor groove through the insertion of arginines in sites where the groove was narrow (Cell, 131:530, 2007). The newest findings, published in (Nature 461:1248, 2009), establish the generality of this mechanism and explain it physical origins. Specifically, short AT rich regions have an intrinsic tendency to narrow grooves and this in turn enhances the negative electrical potential of the DNA in this region, thus attracting positively charged arginines on protein surfaces. These findings are expected to have major impact on our ability to predict the DNA targets of different transcription factors.

Flu cases in early 2009

Because flu viruses mutate nearly once every reproduction cycle, no two people are made sick by precisely the same virus, as illustrated by this chart documenting swine flu cases among humans in early 2009.

The recent outbreak and sudden spread of a novel H1N1 influenza virus has caused a worldwide concern and has tested our ability to respond to major public health challenges. Significant scientific resources have been marshaled to discover the best possible responses against this novel swine origin influenza virus. A group led by Raul Rabadan at the Center for Computational Biology and Bioinformatics, and the Department of Biomedical Informatics at Columbia University has been studying the evolution of influenza viruses and the origins of flu pandemics by analyzing large data sets that contain genomic information.