8qlp: Difference between revisions

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8qlp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qlp OCA], [https://pdbe.org/8qlp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qlp RCSB], [https://www.ebi.ac.uk/pdbsum/8qlp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qlp ProSAT]</span></td></tr>

In both prokaryotic and eukaryotic innate immune systems, TIR domains function as NADases that degrade the key metabolite NAD+ or generate signaling molecules. Catalytic activation of TIR domains requires oligomerization, but how this is achieved varies in distinct immune systems. In the Short prokaryotic Argonaute (pAgo)/TIR-APAZ (SPARTA) immune system, TIR NADase activity is triggered upon guide RNA-mediated recognition of invading DNA by an unknown mechanism. Here, we describe cryo-EM structures of SPARTA in the inactive monomeric and target DNA-activated tetrameric states. The monomeric SPARTA structure reveals that in the absence of target DNA, a C-terminal tail of TIR-APAZ occupies the nucleic acid binding cleft formed by the pAgo and TIR-APAZ subunits, inhibiting SPARTA activation. In the active tetrameric SPARTA complex, guide RNA-mediated target DNA binding displaces the C-terminal tail and induces conformational changes in pAgo that facilitate SPARTA-SPARTA dimerization. Concurrent release and rotation of one TIR domain allow it to form a composite NADase catalytic site with the other TIR domain within the dimer, and generate a self-complementary interface that mediates cooperative tetramerization. Combined, this study provides critical insights into the structural architecture of SPARTA and the molecular mechanism underlying target DNA-dependent oligomerization and catalytic activation.

Target DNA-dependent activation mechanism of the prokaryotic immune system SPARTA.,Finocchio G, Koopal B, Potocnik A, Heijstek C, Westphal AH, Jinek M, Swarts DC Nucleic Acids Res. 2024 Jan 15:gkad1248. doi: 10.1093/nar/gkad1248. PMID:38224450<ref>PMID:38224450</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<references/>

[[Category: Large Structures]]

[[Category: Finocchio G]]

[[Category: Heijstek C]]

[[Category: Jinek M]]

[[Category: Koopal B]]

[[Category: Potocnik A]]

[[Category: Swarts D]]