title: The crystal structure of human Argonaute2.
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.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Nicole T
authors.initials: NT
authors.lastname: Schirle
authors.forename: Ian J
authors.initials: IJ
authors.lastname: MacRae
mesh_terms: D000595:Amino Acid Sequence; D060565:Argonaute Proteins / Q000737:chemistry* / Q000378:metabolism; D020029:Base Pairing; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D014364:Tryptophan / Q000737:chemistry; D058727:RNA, Small Untranslated
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D014364:Tryptophan; D058727:RNA, Small Untranslated