9EWZ
Cryo-EM structure of the E. coli BrxX methyltransferase in complex with DNA
Summary for 9EWZ
| Entry DOI | 10.2210/pdb9ewz/pdb |
| EMDB information | 50027 |
| Descriptor | Adenine-specific methyltransferase BrxX, DNA (26-MER) with BREX binding site GGTAAG, MAGNESIUM ION, ... (5 entities in total) |
| Functional Keywords | methyltransferase, phage defense, brex, transferase |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 3 |
| Total formula weight | 153908.00 |
| Authors | |
| Primary citation | Drobiazko, A.,Adams, M.C.,Skutel, M.,Potekhina, K.,Kotovskaya, O.,Trofimova, A.,Matlashov, M.,Yatselenko, D.,Maxwell, K.L.,Blower, T.R.,Severinov, K.,Ghilarov, D.,Isaev, A. Molecular basis of foreign DNA recognition by BREX anti-phage immunity system. Nat Commun, 16:1825-1825, 2025 Cited by PubMed Abstract: Anti-phage systems of the BREX (BacteRiophage EXclusion) superfamily rely on site-specific epigenetic DNA methylation to discriminate between the host and invading DNA. We demonstrate that in Type I BREX systems, defense and methylation require BREX site DNA binding by the BrxX (PglX) methyltransferase employing S-adenosyl methionine as a cofactor. We determined 2.2-Å cryoEM structure of Escherichia coli BrxX bound to target dsDNA revealing molecular details of BREX DNA recognition. Structure-guided engineering of BrxX expands its DNA specificity and dramatically enhances phage defense. We show that BrxX alone does not methylate DNA, and BREX activity requires an assembly of a supramolecular BrxBCXZ immune complex. Finally, we present a cryoEM structure of BrxX bound to a phage-encoded inhibitor Ocr that sequesters BrxX in an inactive dimeric form. We propose that BrxX-mediated foreign DNA sensing is a necessary first step in activation of BREX defense. PubMed: 39979294DOI: 10.1038/s41467-025-57006-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.22 Å) |
Structure validation
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