8ffi

Structure of tetramerized MapSPARTA upon guide RNA-mediated target DNA binding

spinqualitylabelsall models 8ffi, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ffi is a 16 chain structure with sequence from Maribacter polysiphoniae and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.7Å Ligands: MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A316E683_9FLAO Publication Abstract from PubMed While eukaryotic Argonautes and long prokaryotic Argonautes (pAgos) cleave nucleic acids, some short pAgos lack nuclease activity and hydrolyze NAD(P)(+) to induce bacterial cell death(1). We present a hierarchical activation pathway for SPARTA, a short pAgo consisting of an Ago protein and an associated protein TIR-APAZ(2). SPARTA progresses through distinct oligomeric forms, including a monomeric apo state, a monomeric RNA/DNA-bound state, two dimeric RNA/DNA-bound states, and a tetrameric RNA/DNA-bound active state. These snapshots together identify oligomerization as a mechanistic principle of SPARTA activation. Apo SPARTA is inactive, its RNA/DNA-binding channel occupied an auto-inhibitory motif in TIR-APAZ. Upon RNA/DNA binding, SPARTA transitions from a monomer to a symmetric and then an asymmetric dimer, in which two TIR domains interact via charge and shape complementarity. Next, two dimers assemble into a tetramer with a central TIR cluster responsible for hydrolyzing NAD(P)(+). Additionally, we observed unique features of SPARTA-RNA/DNA interactions, including competition between the DNA 3' end and the auto-inhibitory motif, interactions between the RNA G2 nucleotide and Ago, and splaying of the RNA-DNA duplex by two loops exclusive to short pAgos. Together, our findings contribute a mechanistic basis for the activation of short pAgos, a large section of the Ago superfamily. Oligomerization-mediated activation of a short prokaryotic Argonaute.,Shen Z, Yang XY, Xia S, Huang W, Taylor DJ, Nakanishi K, Fu TM Nature. 2023 Jul 26. doi: 10.1038/s41586-023-06456-z. PMID:37494956 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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