9NV3

Hybrid model of a complex of BREX proteins BrxB and PglZ from Salmonella typhimurium

Summary for 9NV3

• Entry DOI: 10.2210/pdb9nv3/pdb
• EMDB information: 49827
• Descriptor: DUF1788 domain-containing protein, PglZ domain-containing protein (2 entities in total)
• Functional Keywords: restriction, bacteriophage, defense, brex, salmonella typhimurium, salmonella, alphafold, antimicrobial protein
• Biological source: Salmonella enterica subsp. enterica serovar Typhimurium str. D23580; More
• Total number of polymer chains: 2
• Total formula weight: 125532.56

Authors

Doyle, L.A.,Stoddard, B.,Blower, T.R.,Kaiser, B. (deposition date: 2025-03-20, release date: 2025-07-02, Last modification date: 2025-07-09)

Primary citation

Readshaw, J.J.,Doyle, L.A.,Puiu, M.,Kelly, A.,Nelson, A.,Kaiser, A.J.,McGuire, S.F.,Peralta Acosta, J.,Smith, D.L.,Stoddard, B.L.,Kaiser, B.K.,Blower, T.R.
PglZ from Type I BREX phage defence systems is a metal-dependent nuclease that forms a sub-complex with BrxB.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: BREX (Bacteriophage Exclusion) systems, identified through shared identity with Pgl (Phage Growth Limitation) systems, are a widespread, highly diverse group of phage defence systems found throughout bacteria and archaea. The varied BREX Types harbour multiple protein subunits (between four and eight) and all encode a conserved putative phosphatase, PglZ, and an equally conserved, putative ATPase, BrxC. Almost all BREX systems also contain a site-specific methyltransferase, PglX. Despite having determined the structure and fundamental biophysical and biochemical behaviours of several BREX factors (including the PglX methyltransferase, the BrxL effector, the BrxA DNA-binding protein, and a commonly-associated transcriptional regulator, BrxR), the mechanism by which BREX impedes phage replication remains largely undetermined. In this study, we identified a stable BREX sub-complex of PglZ:BrxB, generated and validated a structural model of that protein complex, and assessed the biochemical activity of PglZ from BREX, revealing it to be a metal-dependent nuclease. PglZ can cleave cyclic oligonucleotides, linear oligonucleotides, plasmid DNA and both non-modified and modified linear phage genomes. PglZ nuclease activity has no obvious role in BREX-dependent methylation, but does contribute to BREX phage defence. BrxB binding does not impact PglZ nuclease activity. These data contribute to our growing understanding of BREX phage defence.

PubMed: 40548935
DOI: 10.1093/nar/gkaf540

Experimental method

ELECTRON MICROSCOPY (4.45 Å)