8PS5

Escherichia coli SduA complex bound to DNA

Summary for 8PS5

• Entry DOI: 10.2210/pdb8ps5/pdb
• EMDB information: 17845
• Descriptor: Shedu effector protein, 40 nt DNA substrate (2 entities in total)
• Functional Keywords: sdua, shedu, prokaryotic immune system, immune system
• Biological source: Escherichia coli KTE10; More
• Total number of polymer chains: 6
• Total formula weight: 214484.94

Authors

Loeff, L.,Jinek, M. (deposition date: 2023-07-13, release date: 2025-01-22, Last modification date: 2025-02-19)

Primary citation

Loeff, L.,Walter, A.,Rosalen, G.T.,Jinek, M.
DNA end sensing and cleavage by the Shedu anti-phage defense system.
Cell, 188:721-, 2025

PubMed Abstract: 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.

PubMed: 39742808
DOI: 10.1016/j.cell.2024.11.030

Experimental method

ELECTRON MICROSCOPY (2.84 Å)