6CBD

Crystal Structure of Human Argonaute2 Bound to Three Tryptophans

6CBD の概要

• エントリーDOI: 10.2210/pdb6cbd/pdb
• 分子名称: Protein argonaute-2, Guide RNA, Target RNA, ... (7 entities in total)
• 機能のキーワード: gw182, microrna, mirna, mirisc, rna binding protein
• 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: 108330.13

構造登録者

Sheu-Gruttadauria, J.,MacRae, I.J. (登録日: 2018-02-02, 公開日: 2018-04-18, 最終更新日: 2024-03-13)

主引用文献

Sheu-Gruttadauria, J.,MacRae, I.J.
Phase Transitions in the Assembly and Function of Human miRISC.
Cell, 173:946-, 2018

PubMed Abstract: miRISC is a multi-protein assembly that uses microRNAs (miRNAs) to identify mRNAs targeted for repression. Dozens of miRISC-associated proteins have been identified, and interactions between many factors have been examined in detail. However, the physical nature of the complex remains unknown. Here, we show that two core protein components of human miRISC, Argonaute2 (Ago2) and TNRC6B, condense into phase-separated droplets in vitro and in live cells. Phase separation is promoted by multivalent interactions between the glycine/tryptophan (GW)-rich domain of TNRC6B and three evenly spaced tryptophan-binding pockets in the Ago2 PIWI domain. miRISC droplets formed in vitro recruit deadenylation factors and sequester target RNAs from the bulk solution. The condensation of miRISC is accompanied by accelerated deadenylation of target RNAs bound to Ago2. The combined results may explain how miRISC silences mRNAs of varying size and structure and provide experimental evidence that protein-mediated phase separation can facilitate an RNA processing reaction.

PubMed: 29576456
DOI: 10.1016/j.cell.2018.02.051

実験手法

X-RAY DIFFRACTION (2.203 Å)