4kre
From Proteopedia
Structure of Human Argonaute-1 bound to endogenous Sf9 RNA
Structural highlights
FunctionAGO1_HUMAN Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs).[1] [2] [3] Publication Abstract from PubMedArgonautes are the central protein component in small RNA silencing pathways. Of the four human Argonautes (hAgo1-hAgo4) only hAgo2 is an active slicer. We determined the structure of hAgo1 bound to endogenous copurified RNAs to 1.75 A resolution and hAgo1 loaded with let-7 microRNA to 2.1 A. Both structures are strikingly similar to the structures of hAgo2. A conserved catalytic tetrad within the PIWI domain of hAgo2 is required for its slicing activity. Completion of the tetrad, combined with a mutation on a loop adjacent to the active site of hAgo1, results in slicer activity that is substantially enhanced by swapping in the N domain of hAgo2. hAgo3, with an intact tetrad, becomes an active slicer by swapping the N domain of hAgo2 without additional mutations. Intriguingly, the elements that make Argonaute an active slicer involve a sophisticated interplay between the active site and more distant regions of the enzyme. The making of a slicer: activation of human argonaute-1.,Faehnle CR, Elkayam E, Haase AD, Hannon GJ, Joshua-Tor L Cell Rep. 2013 Jun 27;3(6):1901-9. doi: 10.1016/j.celrep.2013.05.033. Epub 2013, Jun 6. PMID:23746446[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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