Multivalent Recruitment of Human Argonaute by GW182

被引：65

作者：

Elkayam, Elad ^{[1
]}

Faehnle, Christopher R. ^{[1
]}

Morales, Marjorie ^{[1
,3
]}

Sun, Jingchuan ^{[2
,4
]}

Li, Huilin ^{[2
,5
]}

Joshua-Tor, Leemor ^{[1
]}

机构：

[1] Cold Spring Harbor Lab, Howard Hughes Med Inst, Keck Struct Biol Lab, Cold Spring Harbor, NY 11724 USA

[2] Brookhaven Natl Lab, Dept Biochem & Cell Biol, Upton, NY 11973 USA

[3] Cold Spring Harbor Lab, Undergrad Res Program, POB 100, Cold Spring Harbor, NY 11724 USA

[4] Univ Penn, Sch Med, Electron Microscopy Resource Lab, Philadelphia, PA 19104 USA

[5] Van Andel Res Inst, CryoEM Struct Biol Lab, Grand Rapids, MI 49503 USA

来源：

MOLECULAR CELL | 2017年 / 67卷 / 04期

基金：

美国能源部; 美国国家科学基金会;

关键词：

MESSENGER-RNA DEGRADATION; CCR4-NOT DEADENYLASE; PROTEIN COMPLEXES; CRYSTAL-STRUCTURE; BINDING; REPRESSION; REQUIRES; FEATURES; DOMAINS; SITES;

D O I：

10.1016/j.molcel.2017.07.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In miRNA-mediated gene silencing, the physical interaction between human Argonaute (hAgo) and GW182 (hGW182) is essential for facilitating the downstream silencing of the targeted mRNA. GW182 can interact with hAgo via three of the GW/WG repeats in its Argonaute-binding domain: motif-1, motif-2, and the hook motif. The structure of hAgo1 in complex with the hook motif of hGW182 reveals a "gate''-like interaction that is critical for GW182 docking into one of hAgo1's tryptophan-binding pockets. We show that hAgo1 and hAgo2 have a single GW182-binding site and that miRNA binding increases hAgo's affinity to GW182. With target binding occurring rapidly, this ensures that only mature RISC would be recruited for silencing. Finally, we show that hGW182 can recruit up to three copies of hAgo via its three GW motifs. This may explain the observed cooperativity in miRNA-mediated gene silencing.

引用

页码：646 / +

页数：16

共 48 条

[11] Reiterated WG/GW motifs form functionally and evolutionarily conserved ARGONAUTE-binding platforms in RNAi-related components [J].