5w6v
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(New page: ==The Structure of human Argonaute-1 in complex with the hook motif of human GW182== <StructureSection load='5w6v' size='340' side='right' caption='5w6v, resolution 2.8...)
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Revision as of 11:10, 24 August 2017
proteopedia linkproteopedia linkThe Structure of human Argonaute-1 in complex with the hook motif of human GW182
Structural highlights
Function[AGO1_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] [TNR6A_HUMAN] Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs). Required for miRNA-dependent repression of translation and for siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins. As scaffoldng protein associates with argonaute proteins bound to partially complementary mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase complexes.[4] [5] [6] [7] [8] [9] Publication Abstract from PubMedIn miRNA-mediated gene silencing, the physical interaction between human Argonaute (hAgo) and GW182 (hGW182) is essential for facilitating the downstream silencing of the targeted mRNA. GW182 can interact with hAgo via three of the GW/WG repeats in its Argonaute-binding domain: motif-1, motif-2, and the hook motif. The structure of hAgo1 in complex with the hook motif of hGW182 reveals a "gate"-like interaction that is critical for GW182 docking into one of hAgo1's tryptophan-binding pockets. We show that hAgo1 and hAgo2 have a single GW182-binding site and that miRNA binding increases hAgo's affinity to GW182. With target binding occurring rapidly, this ensures that only mature RISC would be recruited for silencing. Finally, we show that hGW182 can recruit up to three copies of hAgo via its three GW motifs. This may explain the observed cooperativity in miRNA-mediated gene silencing. Multivalent Recruitment of Human Argonaute by GW182.,Elkayam E, Faehnle CR, Morales M, Sun J, Li H, Joshua-Tor L Mol Cell. 2017 Aug 17;67(4):646-658.e3. doi: 10.1016/j.molcel.2017.07.007. Epub, 2017 Aug 3. PMID:28781232[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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