Sam Went samuel.c.went@durham.ac.uk
Post Doctoral Research Associate
Structure and rational engineering of the PglX methyltransferase and specificity factor for BREX phage defence
Went, Sam C.; Picton, David M.; Morgan, Richard D.; Nelson, Andrew; Brady, Aisling; Mariano, Giuseppina; Dryden, David T. F.; Smith, Darren L.; Wenner, Nicolas; Hinton, Jay C. D.; Blower, Tim R.
Authors
David Picton david.m.picton@durham.ac.uk
PGR Student Doctor of Philosophy
Richard D. Morgan
Andrew Nelson
Aisling Brady
Giuseppina Mariano
Dr David Dryden david.t.dryden@durham.ac.uk
Assistant Professor
Darren L. Smith
Nicolas Wenner
Jay C. D. Hinton
Professor Tim Blower timothy.blower@durham.ac.uk
Professor
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.
Citation
Went, S. C., Picton, D. M., Morgan, R. D., Nelson, A., Brady, A., Mariano, G., Dryden, D. T. F., Smith, D. L., Wenner, N., Hinton, J. C. D., & Blower, T. R. (2024). Structure and rational engineering of the PglX methyltransferase and specificity factor for BREX phage defence. Nature Communications, 15, Article 7236. https://doi.org/10.1038/s41467-024-51629-7
Journal Article Type | Article |
---|---|
Acceptance Date | Aug 12, 2024 |
Online Publication Date | Aug 22, 2024 |
Publication Date | Aug 22, 2024 |
Deposit Date | Aug 27, 2024 |
Publicly Available Date | Aug 27, 2024 |
Journal | Nature Communications |
Electronic ISSN | 2041-1723 |
Publisher | Nature Research |
Peer Reviewed | Peer Reviewed |
Volume | 15 |
Article Number | 7236 |
DOI | https://doi.org/10.1038/s41467-024-51629-7 |
Public URL | https://durham-repository.worktribe.com/output/2768062 |
Files
Published Journal Article
(8.6 Mb)
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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
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