8isz | pdb_00008isz

Structure of procaryotic Ago with DNA-RNA complex

spinqualitylabelsall models 8isz, resolution 3.27Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8isz is a 4 chain structure with sequence from Thermoflavifilum thermophilum and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.27Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A1I7NFD7_9BACT Publication Abstract from PubMed Argonaute (Ago) mediates RNA or DNA guided inhibition of nucleic acids(1,2). Although the mechanisms underlying eukaryotic (eAgos) and long prokaryotic Ago (pAgos) proteins are known, that of short pAgos remains elusive. Here, we determined cryo-EM structures of short pAgo and the associated TIR-APAZ proteins (SPARTA) from Crenotalea thermophila (Crt): a free-state Crt-SPARTA (3.27 A), a guide RNA / target DNA loaded Crt-SPARTA (3.27 A), two Crt-SPARTA dimers with distinct TIR organization (3.49 A and 3.50 A), and a Crt-SPARTA tetramer (3.41 A). These structures reveal that the Crt-SPARTA is composed of a bilobal-fold Ago lobe connecting with a TIR lobe. Whereas the Crt-Ago harbors a MID and a PIWI domains, Crt-TIR-APAZ harbors a TIR, a N-like, a Linker and a Trigger domains. The bound RNA/DNA duplex adopts a B-form conformation that is recognized by base-specific contacts. Nucleic acid binding causes conformational changes because the Trigger acts as a roadblock preventing the guide RNA 5'- and the target DNA 3'-ends from reaching their canonical pockets, which disorders the MID domain and promotes Crt-SPARTA dimerization. Two RNA/DNA-loaded Crt-SPARTA dimers form a tetramer through their TIR domains. Four Crt-TIR assemble into two parallel, head-to-tail TIR organization, indicating a NADase-active conformation, which is supported by our mutagenesis study. Our results reveal the structural basis of short pAgos in defensing invading nucleic acids and provide insights for optimizing SPARTA-based programmable DNA sequences detection. Nucleic acid-triggered NADase activation of a short prokaryotic Argonaute.,Gao X, Shang K, Zhu K, Wang L, Mu Z, Fu X, Yu X, Qin B, Zhu H, Ding W, Cui S Nature. 2023 Oct 2. doi: 10.1038/s41586-023-06665-6. PMID:37783228 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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