8JAY

CrtSPARTA Octamer bound with guide-target

8JAY の概要

• エントリーDOI: 10.2210/pdb8jay/pdb
• EMDBエントリー: 36138
• 分子名称: 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)
• 機能のキーワード: sparta, ago, tir, dna binding protein/dna/rna, dna binding protein-dna-rna complex
• 由来する生物種: Thermoflavifilum thermophilum; 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 503651.34

構造登録者

Guo, L.J.,Huang, P.P.,Li, Z.X.,Xiao, Y.B.,Chen, M.R. (登録日: 2023-05-07, 公開日: 2024-03-20, 最終更新日: 2024-04-10)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (4.2 Å)