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-Structure paper
| タイトル | Molecular basis of foreign DNA recognition by BREX anti-phage immunity system. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 1825, Year 2025 |
| 掲載日 | 2025年2月20日 |
著者 | Alena Drobiazko / Myfanwy C Adams / Mikhail Skutel / Kristina Potekhina / Oksana Kotovskaya / Anna Trofimova / Mikhail Matlashov / Daria Yatselenko / Karen L Maxwell / Tim R Blower / Konstantin Severinov / Dmitry Ghilarov / Artem Isaev / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:39979294 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.22 - 3.9 Å |
| 構造データ | EMDB-50027, PDB-9ewz: ![]() EMDB-50028: Focused map for NTD and MTD domains of the phage immunity methyltransferase protein BrxX. ![]() EMDB-50029: Consensus map for the phage immunity methyltransferase protein BrxX EMDB-50032, PDB-9ex7: EMDB-50038, PDB-9exh: |
| 化合物 | ![]() ChemComp-MG: ![]() ChemComp-SAM: |
| 由来 |
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キーワード | TRANSFERASE / Methyltransferase / phage defense / BREX / DNA-binding / DNA binding |
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escherichia phage t7 (ファージ)
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