A new preprint from our lab (HERE). We investigate the biophysics and the possible evolutionary history that changed the DNA-binding specificity of bacterial chromosome maintenance proteins (ParB and Noc).

Combining ChIP-seq, X-ray crystallography, and systematic scanning mutagenesis, we show that DNA-binding specificities of ParB and Noc are encoded by a minimal set of just four specificity-defining residues.

Using deep mutational scanning (B1H-seq) and network reconstruction, we show that having the correct mutations is not enough, but that they must also be introduced in a defined order to change DNA-binding specificity.

Some stats: 2 X-ray co-crystal structures, 21 ChIP-seq datasets, 65 purified proteins/variants, and approx. ~100,000 protein variants assayed in parallel (B1H-seq). Lots of work from our PhD student Adam Jalal, Ngat Tran, and the biophysical platform at the JIC.