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-Structure paper
| タイトル | The structural basis for RNA slicing by human Argonaute2. |
|---|---|
| ジャーナル・号・ページ | Cell Rep, Vol. 44, Issue 1, Page 115166, Year 2025 |
| 掲載日 | 2025年1月28日 |
著者 | Abdallah A Mohamed / Peter Y Wang / David P Bartel / Seychelle M Vos / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Cell Rep / PubMed:39932188 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.3 Å |
| 構造データ | EMDB-45752, PDB-9cmp: ![]() EMDB-45753: The structural basis for RNA slicing by human Argonatue2 (Map 1) |
| 化合物 | ![]() ChemComp-MG: |
| 由来 |
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キーワード | HYDROLASE/RNA / RNAi / Argonaute / Slicing / HYDROLASE-RNA complex |
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