9CMP

Structure of human Argonaute2-guide-target complex in a fully paired, slicing-competent conformation

9CMP の概要

• エントリーDOI: 10.2210/pdb9cmp/pdb
• EMDBエントリー: 45752
• 分子名称: RNA (5'-R(P*UP*GP*GP*AP*AP*GP*AP*CP*UP*AP*GP*UP*GP*AP*UP*UP*UP*UP*GP*UP*U)-3'), RNA (5'-R(*CP*AP*AP*CP*AP*AP*AP*AP*UP*CP*AP*CP*UP*AP*GP*UP*CP*UP*UP*CP*CP*A)-3'), Protein argonaute-2, ... (4 entities in total)
• 機能のキーワード: rnai, argonaute, slicing, hydrolase-rna complex, hydrolase/rna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 113234.87

構造登録者

Mohamed, A.A.,Wang, P.Y.,Bartel, D.P.,Vos, S.M. (登録日: 2024-07-15, 公開日: 2024-12-11, 最終更新日: 2025-05-14)

主引用文献

Mohamed, A.A.,Wang, P.Y.,Bartel, D.P.,Vos, S.M.
The structural basis for RNA slicing by human Argonaute2.
Cell Rep, 44:115166-115166, 2025

PubMed Abstract: Argonaute (AGO) proteins associate with guide RNAs to form complexes that slice transcripts that pair to the guide. This slicing drives post-transcriptional gene silencing through RNA interference (RNAi), which is essential for many eukaryotes and the basis for new clinical therapies. Despite this importance, structural information on eukaryotic AGOs in a fully paired, slicing-competent conformation-hypothesized to be intrinsically unstable-has been lacking. Here, we present the cryogenic electron microscopy structure of a human AGO-guide complex bound to a fully paired target, revealing structural rearrangements that enable this conformation. Critically, the N domain of AGO rotates to allow the RNA full access to the central channel and forms contacts that license rapid slicing. Moreover, a conserved loop in the PIWI domain secures the RNA near the active site to enhance slicing rate and specificity. These results explain how AGO accommodates targets possessing pairing specificity typically observed in biological and clinical slicing substrates.

PubMed: 39932188
DOI: 10.1016/j.celrep.2024.115166

実験手法

ELECTRON MICROSCOPY (3.3 Å)