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-Structure paper
| タイトル | A DNA-gated molecular guard controls bacterial Hailong anti-phage defence. |
|---|---|
| ジャーナル・号・ページ | Nature, Vol. 643, Issue 8072, Page 794-800, Year 2025 |
| 掲載日 | 2025年4月30日 |
著者 | Joel M J Tan / Sarah Melamed / Joshua C Cofsky / Deepsing Syangtan / Samuel J Hobbs / Josefina Del Mármol / Marco Jost / Andrew C Kruse / Rotem Sorek / Philip J Kranzusch / ![]() |
| PubMed 要旨 | Animal and bacterial cells use nucleotidyltransferase (NTase) enzymes to respond to viral infection and control major forms of immune signalling including cGAS-STING innate immunity and CBASS anti- ...Animal and bacterial cells use nucleotidyltransferase (NTase) enzymes to respond to viral infection and control major forms of immune signalling including cGAS-STING innate immunity and CBASS anti-phage defence. Here we discover a family of bacterial defence systems, which we name Hailong, that use NTase enzymes to constitutively synthesize DNA signals and guard against phage infection. Hailong protein B (HalB) is an NTase that converts deoxy-ATP into single-stranded DNA oligomers. A series of X-ray crystal structures define a stepwise mechanism of HalB DNA synthesis initiated by a C-terminal tyrosine residue that enables de novo enzymatic priming. We show that HalB DNA signals bind to and repress activation of a partnering Hailong protein A (HalA) effector complex. A 2.0-Å cryo-electron microscopy structure of the HalA-DNA complex reveals a membrane protein with a conserved ion channel domain and a unique crown domain that binds the DNA signal and gates activation. Analysing Hailong defence in vivo, we demonstrate that viral DNA exonucleases required for phage replication trigger release of the primed HalA complex and induce protective host cell growth arrest. Our results explain how inhibitory nucleotide immune signals can serve as molecular guards against phage infection and expand the mechanisms NTase enzymes use to control antiviral immunity. |
リンク | Nature / PubMed:40306316 / PubMed Central |
| 手法 | EM (単粒子) / X線回折 |
| 解像度 | 1.88 - 2.41 Å |
| 構造データ | EMDB-49920: Structure of Hailong HalA in complex with oligodeoxyadenylate ![]() PDB-9dbh: ![]() PDB-9dbi: ![]() PDB-9dbj: |
| 化合物 | ![]() ChemComp-MN: ![]() ChemComp-HOH: ![]() ChemComp-PO4: ![]() PDB-1a3g: ![]() ChemComp-F2A: ![]() PDB-1a3h: ![]() ChemComp-D5M: |
| 由来 |
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キーワード | ANTIVIRAL PROTEIN/DNA / Hailong / nucleotidyltransferase / oligodeoxyadenylate / anti-phage defense / ANTIVIRAL PROTEIN / ANTIVIRAL PROTEIN-DNA complex / ion channel |
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rhodobacteraceae bacterium qy30 (バクテリア)
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