Evidence map›Paper›PMID 39174540›Full record

ArticleNature communications2024

Structure and rational engineering of the PglX methyltransferase and specificity factor for BREX phage defence.

Sam C Went, David M Picton, Richard D Morgan, Andrew Nelson, Aisling Brady, Giuseppina Mariano, David T F Dryden, Darren L Smith, Nicolas Wenner, Jay C D Hinton and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Genomic islands inNAR genomics and bioinformatics · 2025
    Article
  10. Modified DNA substrate selectivity by GmrSD-family Type IV restriction enzyme BrxU.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
    Article
  11. Article
  12. Article
  13. Two novel phages infectingFrontiers in microbiology · 2025
    Article
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

11 authors.

Sam C WentDepartment of Biosciences, Durham University, South Road, Durham, UK.ORCID 0009-0007-5500-7196
David M PictonDepartment of Biosciences, Durham University, South Road, Durham, UK.
Richard D MorganNew England Biolabs, 240 County Road, Ipswich, MA, USA.
Andrew NelsonFaculty of Health and Life Sciences, Northumbria University, Newcastle Upon Tyne, UK.
Aisling BradyInstitute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.ORCID 0000-0001-5177-4813
Giuseppina MarianoDepartment of Microbial Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.ORCID 0000-0003-1197-2123
David T F DrydenDepartment of Biosciences, Durham University, South Road, Durham, UK.
Darren L SmithFaculty of Health and Life Sciences, Northumbria University, Newcastle Upon Tyne, UK.ORCID 0000-0003-4925-467X
Nicolas WennerInstitute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
Jay C D HintonInstitute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.ORCID 0000-0003-2671-6026
Tim R BlowerDepartment of Biosciences, Durham University, South Road, Durham, UK. timothy.blower@durham.ac.uk.ORCID 0000-0002-7390-6458

Funding

Lister Institute of Preventive Medicine NARCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/M011186/1RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/X003051/1RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/Y003659/1RCUK | Engineering and Physical Sciences Research Council (EPSRC) EP/S022791/1Wellcome TrustWellcome Trust (Wellcome) 106914/Z/15/ZWellcome Trust (Wellcome) 218622/Z/19/Z
6 · The paper itself

Abstract

Bacteria have evolved a broad range of systems that provide defence against their viral predators, bacteriophages. Bacteriophage Exclusion (BREX) systems recognise and methylate 6 bp non-palindromic motifs within the host genome, and prevent replication of non-methylated phage DNA that encodes these same motifs. How BREX recognises cognate motifs has not been fully understood. In this study we characterise BREX from pathogenic Salmonella and present X-ray crystallographic structures of the conserved BREX protein, PglX. The PglX N-terminal domain encodes the methyltransferase, whereas the C-terminal domain is for motif recognition. We also present the structure of PglX bound to the phage-derived DNA mimic, Ocr, an inhibitor of BREX activity. Our analyses propose modes for DNA-binding by PglX and indicate that both methyltransferase activity and defence require larger BREX complexes. Through rational engineering of PglX we broaden both the range of phages targeted, and the host motif sequences that are methylated by BREX. Our data demonstrate that PglX is used to recognise specific DNA sequences for BREX activity, contributing to motif recognition for both phage defence and host methylation.

Indexed as

BacteriophagesMethyltransferasesBacterial ProteinsCrystallography, X-RayDNA MethylationDNA, ViralModels, MolecularSalmonellaBacterial ProteinsDNA, ViralMethyltransferases

Identifiers

PMID39174540
PMCPMC11341690

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Registered trials

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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.