Evidence map›Paper›PMID 40301632›Full record

ArticleCommunications biology2025

Allosteric activation mechanism of DriD, a WYL-domain containing transcription regulator.

Emily Cannistraci, Bindu Y Srinivasu, Jose Chavez Orozco, Kevin Gozzi, Thomas E Wales, Maria A Schumacher

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Emily Cannistraci *Department of Biochemistry, 307 Research Dr., Box 3711, Duke University Medical Center, Durham, NC, 27710, USA.ORCID http://orcid.org/0000-0003-1880-9185
Bindu Y Srinivasu *Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA.
Jose Chavez OrozcoDepartment of Biochemistry, 307 Research Dr., Box 3711, Duke University Medical Center, Durham, NC, 27710, USA.ORCID http://orcid.org/0009-0007-7617-0371
Kevin Gozzi100 Edwin H Land Blvd, Harvard University Cambridge, Cambridge, MA, 02142, USA.
Thomas E WalesDepartment of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA. t.wales@northeastern.edu.ORCID http://orcid.org/0000-0001-6133-5689
Maria A SchumacherDepartment of Biochemistry, 307 Research Dr., Box 3711, Duke University Medical Center, Durham, NC, 27710, USA. Maria.Schumacher@Duke.edu.ORCID http://orcid.org/0000-0002-5264-1120

Funding

User Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI PAUL David ADAMS, Gregory L Hura · 2017 to 2026
$28.6M
Deciphering fundamental biological processes involving protein-nucleic acid interactions at the molecular levelR35GM130290 · NIGMS · DUKE UNIVERSITY · PI Maria Schumacher · 2019 to 2026
$4.9M
Conformational Regulation and Therapeutic Targeting of Oncogenic KRASR01CA233978 · NCI · NORTHEASTERN UNIVERSITY · PI WALENSKY, LOREN DAVID, WALES, THOMAS EDWARD · 2020 to 2024
$2.4M
NCI NIH HHS R01 CA233978NIGMS NIH HHS P30 GM124169NIGMS NIH HHS R35 GM130290U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM130290
6 · The paper itself

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.

Indexed as

Bacterial ProteinsCaulobacter crescentusTranscription FactorsAllosteric RegulationDNA-Binding ProteinsDNA, Single-StrandedGene Expression Regulation, BacterialModels, MolecularProtein BindingProtein DomainsProtein MultimerizationBacterial ProteinsDNA-Binding ProteinsDNA, Single-StrandedTranscription Factors

Identifiers

PMID40301632
PMCPMC12041258

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.