Nucleic acid mediated activation of a short prokaryotic Argonaute immune system
Year: 2024
Type: article
Abstract: A short prokaryotic Argonaute (pAgo) TIR-APAZ (SPARTA) defense system, activated by invading DNA to unleash its TIR domain for NAD(P) + hydrolysis, was recently identified in bacteria. We report the crystal structure of SPARTA heterodimer in the absence of guide-RNA/target-ssDNA (2.66 Å) and a cryo-EM structure of the SPARTA oligomer (tetramer of heterodimers) bound to guide-RNA/target-ssDNA at nominal 3.15–3.35 Å resolution. The crystal structure provides a high-resolution view of SPARTA, revealing the APAZ domain as equivalent to the N, L1, and L2 regions of long pAgos and the MID domain containing a unique insertion (insert57). Cryo-EM structure reveals regions of the PIWI (loop10-9) and APAZ (helix αN) domains that reconfigure for nucleic-acid binding and decrypts regions/residues that reorganize to expose a positively charged pocket for higher-order assembly. The TIR domains amass in a parallel-strands arrangement for catalysis. We visualize SPARTA before and after RNA/ssDNA binding and uncover the basis of its active assembly leading to abortive infection.
Source: Nature Communications
Institution: Icahn School of Medicine at Mount Sinai
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: U.S. Department of Energy, U.S. Department of Health and Human Services, Agouron Institute, National Institutes of Health, Office of Science, University of California, San Francisco, National Institute of General Medical Sciences, National Center for Research Resources, Biological and Environmental Research, Brookhaven National Laboratory
Awards: National Resource for Automated Molecular Microscopy, G1285306620, G1353251002, Acquisition of Detector for JEOL 3200 FSC Electron Microscope, G1867732070, G2004402655, G241279073, G2776070826, G3067052642, G3262563802, Resource for Biocomputing Visualization and Informatics, G357145406, G3728080647, Dual-Beam Scanning Electron Microscope for New York Structural Biology Center, G4815039349, G5004220402, G533446661, G5765906131, G6476969910, G6816383395, G6985549539, G7463374569, G8701900045, Center for Biomolecular Structure (CBMS), Protein-nucleic acid interactions in basic cellular processes
OpenAlex ID: W4399395070