8JPX

Cryo-EM structure of PfAgo-guide DNA-target DNA complex

8JPX の概要

• エントリーDOI: 10.2210/pdb8jpx/pdb
• EMDBエントリー: 36489
• 分子名称: Protein argonaute, Guide DNA, Target DNA, ... (5 entities in total)
• 機能のキーワード: nuclease, gene regulation
• 由来する生物種: Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 205552.00

構造登録者

Zhuang, L. (登録日: 2023-06-13, 公開日: 2024-01-31, 最終更新日: 2025-07-23)

主引用文献

Wang, L.,Chen, W.,Zhang, C.,Xie, X.,Huang, F.,Chen, M.,Mao, W.,Yu, N.,Wei, Q.,Ma, L.,Li, Z.
Molecular mechanism for target recognition, dimerization, and activation of Pyrococcus furiosus Argonaute.
Mol.Cell, 84:675-686.e4, 2024

PubMed Abstract: The Argonaute nuclease from the thermophilic archaeon Pyrococcus furiosus (PfAgo) contributes to host defense and represents a promising biotechnology tool. Here, we report the structure of a PfAgo-guide DNA-target DNA ternary complex at the cleavage-compatible state. The ternary complex is predominantly dimerized, and the dimerization is solely mediated by PfAgo at PIWI-MID, PIWI-PIWI, and PAZ-N interfaces. Additionally, PfAgo accommodates a short 14-bp guide-target DNA duplex with a wedge-type N domain and specifically recognizes 5'-phosphorylated guide DNA. In contrast, the PfAgo-guide DNA binary complex is monomeric, and the engagement of target DNA with 14-bp complementarity induces sufficient dimerization and activation of PfAgo, accompanied by movement of PAZ and N domains. A closely related Argonaute from Thermococcus thioreducens adopts a similar dimerization configuration with an additional zinc finger formed at the dimerization interface. Dimerization of both Argonautes stabilizes the catalytic loops, highlighting the important role of Argonaute dimerization in the activation and target cleavage.

PubMed: 38295801
DOI: 10.1016/j.molcel.2024.01.004

実験手法

ELECTRON MICROSCOPY (2.9 Å)