4Z4I

Human Argonaute2 A481T Mutant Bound to t1-G Target RNA

4Z4I の概要

• エントリーDOI: 10.2210/pdb4z4i/pdb
• 関連するPDBエントリー: 4Z4C 4Z4D 4Z4E 4Z4F 4Z4G 4Z4H
• 分子名称: Protein argonaute-2, RNA (5'-R(P*UP*UP*CP*AP*CP*AP*UP*UP*GP*CP*CP*CP*AP*AP*GP*UP*CP*UP*UP*U)-3'), RNA (5'-R(*CP*AP*AP*UP*GP*UP*GP*A)-3'), ... (6 entities in total)
• 機能のキーワード: argonaute2, gene regulation-rna complex, gene regulation/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: 107865.53

構造登録者

Schirle, N.T.,MacRae, I.J. (登録日: 2015-04-02, 公開日: 2015-09-23, 最終更新日: 2023-09-27)

主引用文献

Schirle, N.T.,Sheu-Gruttadauria, J.,Chandradoss, S.D.,Joo, C.,MacRae, I.J.
Water-mediated recognition of t1-adenosine anchors Argonaute2 to microRNA targets.
Elife, 4:-, 2015

PubMed Abstract: MicroRNAs (miRNAs) direct post-transcriptional regulation of human genes by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. An enigmatic feature of many conserved mammalian miRNA target sites is that an adenosine (A) nucleotide opposite miRNA nucleotide-1 confers enhanced target repression independently of base pairing potential to the miRNA. In this study, we show that human Argonaute2 (Ago2) possesses a solvated surface pocket that specifically binds adenine nucleobases in the 1 position (t1) of target RNAs. t1A nucleotides are recognized indirectly through a hydrogen-bonding network of water molecules that preferentially interacts with the N6 amine on adenine. t1A nucleotides are not utilized during the initial binding of Ago2 to its target, but instead function by increasing the dwell time on target RNA. We also show that N6 adenosine methylation blocks t1A recognition, revealing a possible mechanism for modulation of miRNA target site potency.

PubMed: 26359634
DOI: 10.7554/eLife.07646

実験手法

X-RAY DIFFRACTION (2.801 Å)