SNAP annotations: PDB entry 6y93

PDB-id

6y93; DSSR-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein

Method

X-ray (2.23 Å)

Summary

Crystal structure of the DNA-binding domain of the nucleoid occlusion factor (noc) complexed to the noc-binding site (nbs)

Reference

Jalal ASB, Tran NT, Stevenson CE, Chan EW, Lo R, Tan X, Noy A, Lawson DM, Le TBK (2020): "Diversification of DNA-Binding Specificity by Permissive and Specificity-Switching Mutations in the ParB/Noc Protein Family." Cell Rep, 32, 107928. doi: 10.1016/j.celrep.2020.107928.

Abstract

Specific interactions between proteins and DNA are essential to many biological processes. Yet, it remains unclear how the diversification in DNA-binding specificity was brought about, and the mutational paths that led to changes in specificity are unknown. Using a pair of evolutionarily related DNA-binding proteins, each with a different DNA preference (ParB [Partitioning Protein B] and Noc [Nucleoid Occlusion Factor], which both play roles in bacterial chromosome maintenance), we show that specificity is encoded by a set of four residues at the protein-DNA interface. Combining X-ray crystallography and deep mutational scanning of the interface, we suggest that permissive mutations must be introduced before specificity-switching mutations to reprogram specificity and that mutational paths to new specificity do not necessarily involve dual-specificity intermediates. Overall, our results provide insight into the possible evolutionary history of ParB and Noc and, in a broader context, might be useful for understanding the evolution of other classes of DNA-binding proteins.