7ZG6

TacA1 antitoxin

Summary for 7ZG6

• Entry DOI: 10.2210/pdb7zg6/pdb
• Descriptor: DUF1778 domain-containing protein, MAGNESIUM ION (3 entities in total)
• Functional Keywords: salmonella, toxin-antitoxin system, rhh domain, antitoxin
• Biological source: Salmonella enterica subsp. enterica serovar Typhimurium
• Total number of polymer chains: 2
• Total formula weight: 20884.01

Authors

Grabe, G.J.,Morgan, R.M.L.,Helaine, S. (deposition date: 2022-04-01, release date: 2023-10-11, Last modification date: 2024-04-10)

Primary citation

Grabe, G.J.,Giorgio, R.T.,Wieczor, M.,Gollan, B.,Sargen, M.,Orozco, M.,Hare, S.A.,Helaine, S.
Molecular stripping underpins derepression of a toxin-antitoxin system.
Nat.Struct.Mol.Biol., 2024

PubMed Abstract: Transcription factors control gene expression; among these, transcriptional repressors must liberate the promoter for derepression to occur. Toxin-antitoxin (TA) modules are bacterial elements that autoregulate their transcription by binding the promoter in a T:A ratio-dependent manner, known as conditional cooperativity. The molecular basis of how excess toxin triggers derepression has remained elusive, largely because monitoring the rearrangement of promoter-repressor complexes, which underpin derepression, is challenging. Here, we dissect the autoregulation of the Salmonella enterica tacAT3 module. Using a combination of assays targeting DNA binding and promoter activity, as well as structural characterization, we determine the essential TA and DNA elements required to control transcription, and we reconstitute a repression-to-derepression path. We demonstrate that excess toxin triggers molecular stripping of the repressor complex off the DNA through multiple allosteric changes causing DNA distortion and ultimately leading to derepression. Thus, our work provides important insight into the mechanisms underlying conditional cooperativity.

PubMed: 38538913
DOI: 10.1038/s41594-024-01253-2

Experimental method

X-RAY DIFFRACTION (1.95 Å)