5w6v

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The Structure of human Argonaute-1 in complex with the hook motif of human GW182

Structural highlights

5w6v is a 3 chain structure with sequence from Homo sapiens and Spodoptera frugiperda. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.828Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

In 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[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
16 reviews cite this structure
Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation.
O'Brien et al. (2018)
15 more
21 other articles
No citations found

See Also

References

  1. ↑ Meister G, Landthaler M, Peters L, Chen PY, Urlaub H, Luhrmann R, Tuschl T. Identification of novel argonaute-associated proteins. Curr Biol. 2005 Dec 6;15(23):2149-55. Epub 2005 Nov 10. PMID:16289642 doi:10.1016/j.cub.2005.10.048
  2. ↑ Janowski BA, Huffman KE, Schwartz JC, Ram R, Nordsell R, Shames DS, Minna JD, Corey DR. Involvement of AGO1 and AGO2 in mammalian transcriptional silencing. Nat Struct Mol Biol. 2006 Sep;13(9):787-92. Epub 2006 Aug 27. PMID:16936728 doi:nsmb1140
  3. ↑ Wu L, Fan J, Belasco JG. Importance of translation and nonnucleolytic ago proteins for on-target RNA interference. Curr Biol. 2008 Sep 9;18(17):1327-32. doi: 10.1016/j.cub.2008.07.072. PMID:18771919 doi:10.1016/j.cub.2008.07.072
  4. ↑ Elkayam E, Faehnle CR, Morales M, Sun J, Li H, Joshua-Tor L. Multivalent Recruitment of Human Argonaute by GW182. Mol Cell. 2017 Aug 17;67(4):646-658.e3. doi: 10.1016/j.molcel.2017.07.007. Epub, 2017 Aug 3. PMID:28781232 doi:http://dx.doi.org/10.1016/j.molcel.2017.07.007

Contents


PDB ID 5w6v

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