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Science. 2012 May 25;336(6084):1037-40. doi: 10.1126/science.1221551. Epub 2012 Apr 26.

The crystal structure of human Argonaute2.

Author information

1
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Abstract

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.

PMID:
22539551
PMCID:
PMC3521581
DOI:
10.1126/science.1221551
[Indexed for MEDLINE]
Free PMC Article

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