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Auxiliary interfaces support the evolution of specific toxin–antitoxin pairing

DOI: 10.1038/s41589-021-00862-y DOI Help

Authors: Grzegorz J. Grabe (Harvard Medical School) , Rachel T. Giorgio (Harvard Medical School) , Alexander M. J. Hall (Harvard Medical School) , Rhodri M. L. Morgan (Imperial College London) , Laurent Dubois (Harvard Medical School) , Tyler A. Sisley (Harvard Medical School) , Julian A. Rycroft (Harvard Medical School) , Stephen A. Hare (University of Sussex) , Sophie Helaine (Harvard Medical School; Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Chemical Biology , VOL 163

State: Published (Approved)
Published: September 2021
Diamond Proposal Number(s): 17221

Abstract: Toxin–antitoxin (TA) systems are a large family of genes implicated in the regulation of bacterial growth and its arrest in response to attacks. These systems encode nonsecreted toxins and antitoxins that specifically pair, even when present in several paralogous copies per genome. Salmonella enterica serovar Typhimurium contains three paralogous TacAT systems that block bacterial translation. We determined the crystal structures of the three TacAT complexes to understand the structural basis of specific TA neutralization and the evolution of such specific pairing. In the present study, we show that alteration of a discrete structural add-on element on the toxin drives specific recognition by their cognate antitoxin underpinning insulation of the three pairs. Similar to other TA families, the region supporting TA-specific pairing is key to neutralization. Our work reveals that additional TA interfaces beside the main neutralization interface increase the safe space for evolution of pairing specificity.

Journal Keywords: Bacteria; Proteins

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography

Added On: 27/09/2021 15:54

Discipline Tags:

Genetics Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)