8y82

Cryo-EM structure of the tetrameric SPARSA gRNA-ssDNA-NAD+ complex

spinqualitylabelsall models 8y82, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8y82 is a 16 chain structure with sequence from Escherichia coli 'BL21-Gold(DE3)pLysS AG' and Geobacter sulfurreducens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.4Å Ligands: AMP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q74DF6_GEOSL Publication Abstract from PubMed Eukaryotic Argonaute proteins (eAgos) utilize short nucleic acid guides to target complementary sequences for RNA silencing, while prokaryotic Agos (pAgos) provide immunity against invading plasmids or bacteriophages. The Sir2-domain associated short pAgo (SPARSA) immune system defends against invaders by depleting NAD(+) and triggering cell death. However, the molecular mechanism underlying SPARSA activation remains unknown. Here, we present cryo-EM structures of inactive monomeric, active tetrameric and active NAD(+)-bound tetrameric SPARSA complexes, elucidating mechanisms underlying SPARSA assembly, guide RNA preference, target ssDNA-triggered SPARSA tetramerization, and tetrameric-dependent NADase activation. Short pAgos form heterodimers with Sir2-APAZ, favoring short guide RNA with a 5'-AU from ColE-like plasmids. RNA-guided recognition of the target ssDNA triggers SPARSA tetramerization via pAgo- and Sir2-mediated interactions. The resulting tetrameric Sir2 rearrangement aligns catalytic residue H186 for NAD(+) hydrolysis. These insights advance our understanding of Sir2-domain associated pAgos immune systems and should facilitate the development of a short pAgo-associated biotechnological toolbox. Tetramerization-dependent activation of the Sir2-associated short prokaryotic Argonaute immune system.,Cui N, Zhang JT, Li Z, Wei XY, Wang J, Jia N Nat Commun. 2024 Oct 4;15(1):8610. doi: 10.1038/s41467-024-52910-5. PMID:39366953 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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