ArticleCommunications biology2025
Allosteric activation mechanism of DriD, a WYL-domain containing transcription regulator.
Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Magnesium as a conformational gatekeeper of KRAS: Structural dynamics and therapeutic implications.Protein science : a publication of the Protein Society · 2026Article
- Structures of DnaA domain I reveal a dimer conserved across Actinomycetes.Nucleic acids research · 2026Article
- Transcription activation mechanism of a noncanonical DNA damage response pathway by the WYL-activator, DriD.Science advances · 2026Article
- A WYL transcriptional regulator activates the DNA damage response pathway in Acinetobacter species.Nucleic acids research · 2026Article
- An activator regulates the DNA damage response and anti-phage defense networks in Moraxellaceae.Nucleic acids research · 2025Article
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Authors and funding
6 authors.
Funding
Abstract
WYL-domain containing transcription factors regulate fundamental processes in bacterial physiology, yet how these proteins sense cellular cues to elicit an allosteric response is not well understood. Here we describe the allosteric activation mechanism of DriD, a Caulobacter crescentus homodimeric WYL-domain containing transcription regulator that activates a non-canonical DNA damage pathway. DriD senses ssDNA, produced upon DNA damage via interaction with its WYL domain. This stimulates DriD target DNA binding. However, its DNA-binding domains (DNABDs) are 50 Å from the WYL-domains and linked by a three-helix bundle domain (3HB). Using a combination of crystallography, biochemistry, and HDX-MS we unveil an allosteric mechanism whereby an inhibitory interaction, formed between the DriD DNABD and 3HB in the apo form, is freed upon ssDNA binding, allowing target DNA binding. These findings may serve as a model for understanding activation by the large family of homodimeric WYL activators, including those in pathogenic bacteria.
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Registered trials
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