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Diversification of DNA-binding specificity by permissive and specificity-switching mutations in the ParB/Noc protein family

DOI: 10.1016/j.celrep.2020.107928 DOI Help

Authors: Adam S. B. Jalal (John Innes Centre) , Ngat T. Tran (John Innes Centre) , Clare E. Stevenson (John Innes Centre) , Elliot W. Chan (University of York) , Rebecca Lo (John Innes Centre) , Xiao Tan (John Innes Centre) , Agnes Noy (University of York) , David M. Lawson (John Innes Centre) , Tung B. K. Le (John Innes Centre)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Reports , VOL 32

State: Published (Approved)
Published: July 2020
Diamond Proposal Number(s): 18565

Open Access Open Access

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.

Journal Keywords: chromosome segregation; chromosome organization; protein-DNA interaction; DNA-binding specificity; molecular evolution; gene duplication; ParB-parS; Noc-NBS; nucleoid occlusion

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

Added On: 29/07/2020 13:16


Discipline Tags:

Biochemistry Genetics Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)