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-Structure paper
タイトル | DNA end sensing and cleavage by the Shedu anti-phage defense system. |
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ジャーナル・号・ページ | Cell, Vol. 188, Issue 3, Page 721-733.e17, Year 2025 |
掲載日 | 2025年2月6日 |
![]() | Luuk Loeff / Alexander Walter / Gian Tizio Rosalen / Martin Jinek / ![]() |
PubMed 要旨 | The detection of molecular patterns associated with invading pathogens is a hallmark of innate immune systems. Prokaryotes deploy sophisticated host defense mechanisms in innate anti-phage immunity. ...The detection of molecular patterns associated with invading pathogens is a hallmark of innate immune systems. Prokaryotes deploy sophisticated host defense mechanisms in innate anti-phage immunity. Shedu is a single-component defense system comprising a putative nuclease SduA. Here, we report cryoelectron microscopy (cryo-EM) structures of apo- and double-stranded DNA (dsDNA)-bound tetrameric SduA assemblies, revealing that the N-terminal domains of SduA form a clamp that recognizes free DNA ends. End binding positions the DNA over the PD-(D/E)XK nuclease domain, resulting in dsDNA nicking at a fixed distance from the 5' end. The end-directed DNA nicking activity of Shedu prevents propagation of linear DNA in vivo. Finally, we show that phages escape Shedu immunity by suppressing their recombination-dependent DNA replication pathway. Taken together, these results define the antiviral mechanism of Shedu systems, underlining the paradigm that recognition of pathogen-specific nucleic acid structures is a conserved feature of innate immunity across all domains of life. |
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手法 | EM (単粒子) / X線回折 |
解像度 | 2.52 - 2.95 Å |
構造データ | EMDB-17844, PDB-8ps4: EMDB-17845, PDB-8ps5: ![]() PDB-8ps6: |
化合物 | ![]() ChemComp-MG: ![]() ChemComp-SO4: ![]() ChemComp-HOH: |
由来 |
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![]() | IMMUNE SYSTEM / SduA / Shedu / Prokaryotic immune system |