The Crystal Structure of Human Argonaute2

被引:504
作者
Schirle, Nicole T. [1 ]
MacRae, Ian J. [1 ]
机构
[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
关键词
GUIDE RNA; GW182; RECOGNITION; BINDING; DNA; REQUIRES; DOMAIN; DEADENYLASE; MICRORNAS; CLEAVAGE;
D O I
10.1126/science.1221551
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Argonaute proteins form the functional core of the RNA-induced silencing complexes that mediate RNA silencing in eukaryotes. The 2.3 angstrom resolution crystal structure of human Argonaute2 (Ago2) reveals a bilobed molecule with a central cleft for binding guide and target RNAs. Nucleotides 2 to 6 of a heterogeneous mixture of guide RNAs are positioned in an A-form conformation for base pairing with target messenger RNAs. Between nucleotides 6 and 7, there is a kink that may function in microRNA target recognition or release of sliced RNA products. Tandem tryptophan-binding pockets in the PIWI domain define a likely interaction surface for recruitment of glycine-tryptophan-182 (GW182) or other tryptophan-rich cofactors. These results will enable structure-based approaches for harnessing the untapped therapeutic potential of RNA silencing in humans.
引用
收藏
页码:1037 / 1040
页数:4
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