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9CMP

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

Summary for 9CMP
Entry DOI10.2210/pdb9cmp/pdb
EMDB information45752
DescriptorRNA (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)
Functional Keywordsrnai, argonaute, slicing, hydrolase-rna complex, hydrolase/rna
Biological sourceHomo sapiens (human)
More
Total number of polymer chains3
Total formula weight113234.87
Authors
Mohamed, A.A.,Wang, P.Y.,Bartel, D.P.,Vos, S.M. (deposition date: 2024-07-15, release date: 2024-12-11, Last modification date: 2025-02-26)
Primary citationMohamed, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.3 Å)
Structure validation

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PDB entries from 2025-04-02

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