5WEA

Human Argonaute2 Helix-7 Mutant

5WEA の概要

• エントリーDOI: 10.2210/pdb5wea/pdb
• 分子名称: Protein argonaute-2, RNA (5'-R(P*AP*AP*AP*AP*AP*AP*AP*U)-3'), PHENOL, ... (4 entities in total)
• 機能のキーワード: argonaute, rna binding, rna silencing, microrna, hydrolase, 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: 2
• 化学式量合計: 99959.76

構造登録者

Schirle, N.T.,Klum, S.M.,MacRae, I.J. (登録日: 2017-07-08, 公開日: 2017-11-22, 最終更新日: 2023-10-04)

主引用文献

Klum, S.M.,Chandradoss, S.D.,Schirle, N.T.,Joo, C.,MacRae, I.J.
Helix-7 in Argonaute2 shapes the microRNA seed region for rapid target recognition.
EMBO J., 37:75-88, 2018

PubMed Abstract: Argonaute proteins use microRNAs (miRNAs) to identify mRNAs targeted for post-transcriptional repression. Biochemical assays have demonstrated that Argonaute functions by modulating the binding properties of its miRNA guide so that pairing to the seed region is exquisitely fast and accurate. However, the mechanisms used by Argonaute to reshape the binding properties of its small RNA guide remain poorly understood. Here, we identify a structural element, α-helix-7, in human Argonaute2 (Ago2) that is required for speed and fidelity in binding target RNAs. Biochemical, structural, and single-molecule data indicate that helix-7 acts as a molecular wedge that pivots to enforce rapid making and breaking of miRNA:target base pairs in the 3' half of the seed region. These activities allow Ago2 to rapidly dismiss off-targets and dynamically search for seed-matched sites at a rate approaching the limit of diffusion.

PubMed: 28939659
DOI: 10.15252/embj.201796474

実験手法

X-RAY DIFFRACTION (3.12 Å)