8J8H

SPARTA monomer bound with guide-target, state 2

Summary for 8J8H

• Entry DOI: 10.2210/pdb8j8h/pdb
• EMDB information: 36070
• Descriptor: Piwi domain-containing protein, TIR domain-containing protein, RNA (5'-R(P*UP*GP*AP*CP*GP*GP*CP*UP*CP*UP*AP*AP*UP*CP*UP*AP*UP*UP*AP*GP*U)-3'), ... (5 entities in total)
• Functional Keywords: sparta, ago, tir, dna binding protein/dna/rna, dna binding protein-dna-rna complex
• Biological source: Thermoflavifilum thermophilum; More
• Total number of polymer chains: 4
• Total formula weight: 133018.71

Authors

Li, Z.X.,Guo, L.J.,Huang, P.P.,Xiao, Y.B.,Chen, M.R. (deposition date: 2023-05-01, release date: 2024-03-06, Last modification date: 2024-04-10)

Primary citation

Guo, L.,Huang, P.,Li, Z.,Shin, Y.C.,Yan, P.,Lu, M.,Chen, M.,Xiao, Y.
Auto-inhibition and activation of a short Argonaute-associated TIR-APAZ defense system.
Nat.Chem.Biol., 20:512-520, 2024

PubMed Abstract: Short prokaryotic Ago accounts for most prokaryotic Argonaute proteins (pAgos) and is involved in defending bacteria against invading nucleic acids. Short pAgo associated with TIR-APAZ (SPARTA) has been shown to oligomerize and deplete NAD upon guide-mediated target DNA recognition. However, the molecular basis of SPARTA inhibition and activation remains unknown. In this study, we determined the cryogenic electron microscopy structures of Crenotalea thermophila SPARTA in its inhibited, transient and activated states. The SPARTA monomer is auto-inhibited by its acidic tail, which occupies the guide-target binding channel. Guide-mediated target binding expels this acidic tail and triggers substantial conformational changes to expose the Ago-Ago dimerization interface. As a result, SPARTA assembles into an active tetramer, where the four TIR domains are rearranged and packed to form NADase active sites. Together with biochemical evidence, our results provide a panoramic vision explaining SPARTA auto-inhibition and activation and expand understanding of pAgo-mediated bacterial defense systems.

PubMed: 37932527
DOI: 10.1038/s41589-023-01478-0

Experimental method

ELECTRON MICROSCOPY (3.4 Å)