The Structure of Human Argonaute-2 in Complex with miR-20a

被引:445
作者
Elkayam, Elad [1 ,2 ]
Kuhn, Claus-D. [1 ]
Tocilj, Ante [1 ]
Haase, Astrid D.
Greene, Emily M. [1 ,2 ]
Hannon, Gregory J. [2 ]
Joshua-Tor, Leemor [1 ,2 ]
机构
[1] WM Keck Struct Biol Lab, Cold Spring Harbor, NY 11724 USA
[2] Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA
关键词
CRYSTAL-STRUCTURE; SILENCING COMPLEX; RNA RECOGNITION; GUIDE RNA; DOMAIN; RISC; MICRORNAS; BINDING;
D O I
10.1016/j.cell.2012.05.017
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
Argonaute proteins lie at the heart of the RNA-induced silencing complex (RISC), wherein they use small RNA guides to recognize targets. Initial insight into the architecture of Argonautes came from studies of prokaryotic proteins, revealing a crescent-shaped base made up of the amino-terminal, PAZ, middle, and PIWI domains. The recently reported crystal structure of human Argonaute-2 (hAgo2), the "slicer" in RNA interference, in complex with a mixed population of RNAs derived from insect cells provides insight into the architecture of a eukaryotic Argonaute protein with defined biochemical and biological functions. Here, we report the structure of human Ago2 bound to a physiologically relevant microRNA, microRNA-20a, at 2.2 angstrom resolution. The miRNA is anchored at both ends by the Mid and PAZ domains and makes several kinks and turns along the binding groove. Interestingly, miRNA binding confers remarkable stability on hAgo2, locking this otherwise flexible enzyme into a stable conformation.
引用
收藏
页码:100 / 110
页数:11
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