8i87 | pdb_00008i87

Cryo-EM structure of TIR-APAZ/Ago-gRNA-DNA complex

spinqualitylabelsall models 8i87, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8i87 is a 16 chain structure with sequence from Maribacter polysiphoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.1Å Ligands: MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A316E683_9FLAO Publication Abstract from PubMed Nicotinamide adenine dinucleotide (NAD(+)) is a central metabolite in cellular processes. Depletion of NAD(+) has been demonstrated to be a prevalent theme in both prokaryotic and eukaryotic immune responses. Short prokaryotic Argonaute proteins (Agos) are associated with NADase domain-containing proteins (TIR-APAZ or SIR2-APAZ) encoded in the same operon. They confer immunity against mobile genetic elements, such as bacteriophages and plasmids, by inducing NAD(+) depletion upon recognition of target nucleic acids. However, the molecular mechanisms underlying the activation of such prokaryotic NADase/Ago immune systems remain unknown. Here, we report multiple cryo-EM structures of NADase/Ago complexes from two distinct systems (TIR-APAZ/Ago and SIR2-APAZ/Ago). Target DNA binding triggers tetramerization of the TIR-APAZ/Ago complex by a cooperative self-assembly mechanism, while the heterodimeric SIR2-APAZ/Ago complex does not assemble into higher-order oligomers upon target DNA binding. However, the NADase activities of these two systems are unleashed via a similar closed-to-open transition of the catalytic pocket, albeit by different mechanisms. Furthermore, a functionally conserved sensor loop is employed to inspect the guide RNA-target DNA base pairing and facilitate the conformational rearrangement of Ago proteins required for the activation of these two systems. Overall, our study reveals the mechanistic diversity and similarity of Ago protein-associated NADase systems in prokaryotic immune response. Structural insights into mechanisms of Argonaute protein-associated NADase activation in bacterial immunity.,Wang X, Li X, Yu G, Zhang L, Zhang C, Wang Y, Liao F, Wen Y, Yin H, Liu X, Wei Y, Li Z, Deng Z, Zhang H Cell Res. 2023 Jun 13. doi: 10.1038/s41422-023-00839-7. PMID:37311833 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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