+検索条件
-Structure paper
タイトル | Auto-inhibition and activation of a short Argonaute-associated TIR-APAZ defense system. |
---|---|
ジャーナル・号・ページ | Nat Chem Biol, Vol. 20, Issue 4, Page 512-520, Year 2024 |
掲載日 | 2023年11月6日 |
著者 | Lijie Guo / Pingping Huang / Zhaoxing Li / Young-Cheul Shin / Purui Yan / Meiling Lu / Meirong Chen / Yibei Xiao / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Chem Biol / PubMed:37932527 |
手法 | EM (単粒子) |
解像度 | 3.3 - 4.2 Å |
構造データ | EMDB-36059, PDB-8j84: EMDB-36070, PDB-8j8h: EMDB-36095, PDB-8j9g: EMDB-36114, PDB-8j9p: EMDB-36138, PDB-8jay: |
化合物 | ChemComp-MG: |
由来 |
|
キーワード | DNA BINDING PROTEIN / SPARTA / Ago / Tir / DNA BINDING PROTEIN/DNA/RNA / DNA BINDING PROTEIN-DNA-RNA complex / DNA BINDING PROTEIN/RNA/DNA / DNA BINDING PROTEIN-RNA-DNA complex |