|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5vm9' size='340' side='right'caption='[[5vm9]], [[Resolution|resolution]] 3.28Å' scene=''> | | <StructureSection load='5vm9' size='340' side='right'caption='[[5vm9]], [[Resolution|resolution]] 3.28Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vm9]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Insect_cell_expression_vector_ptie1 Insect cell expression vector ptie1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VM9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VM9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vm9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Insect_cell_expression_vector_pTIE1 Insect cell expression vector pTIE1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VM9 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AGO3, EIF2C3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.28Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5vm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vm9 OCA], [http://pdbe.org/5vm9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vm9 RCSB], [http://www.ebi.ac.uk/pdbsum/5vm9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vm9 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5vm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vm9 OCA], [https://pdbe.org/5vm9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vm9 RCSB], [https://www.ebi.ac.uk/pdbsum/5vm9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vm9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AGO3_HUMAN AGO3_HUMAN]] Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Proposed to be involved in stabilization of small RNA derivates (riRNA) derived from processed RNA polymerase III-transcribed Alu repeats containing a DR2 retinoic acid response element (RARE) in stem cells and in the subsequent riRNA-dependent degradation of a subset of RNA polymerase II-transcribed coding mRNAs by recruiting a mRNA decapping complex involving EDC4.[HAMAP-Rule:MF_03032]<ref>PMID:18771919</ref> <ref>PMID:23064648</ref> | + | [https://www.uniprot.org/uniprot/AGO3_HUMAN AGO3_HUMAN] Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Proposed to be involved in stabilization of small RNA derivates (riRNA) derived from processed RNA polymerase III-transcribed Alu repeats containing a DR2 retinoic acid response element (RARE) in stem cells and in the subsequent riRNA-dependent degradation of a subset of RNA polymerase II-transcribed coding mRNAs by recruiting a mRNA decapping complex involving EDC4.[HAMAP-Rule:MF_03032]<ref>PMID:18771919</ref> <ref>PMID:23064648</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 26: |
Line 26: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Insect cell expression vector ptie1]] | + | [[Category: Insect cell expression vector pTIE1]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Nakanishi, K]] | + | [[Category: Nakanishi K]] |
| - | [[Category: Park, M S]] | + | [[Category: Park MS]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Hydrolase-rna complex]]
| + | |
| - | [[Category: Protein]]
| + | |
| - | [[Category: Rna binding protein-rna complex]]
| + | |
| Structural highlights
Function
AGO3_HUMAN Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Proposed to be involved in stabilization of small RNA derivates (riRNA) derived from processed RNA polymerase III-transcribed Alu repeats containing a DR2 retinoic acid response element (RARE) in stem cells and in the subsequent riRNA-dependent degradation of a subset of RNA polymerase II-transcribed coding mRNAs by recruiting a mRNA decapping complex involving EDC4.[HAMAP-Rule:MF_03032][1] [2]
Publication Abstract from PubMed
Of the four human Argonaute (AGO) paralogs, only AGO2 has been shown to have slicer activity. The others (AGO1, AGO3 and AGO4) have been thought to assemble with microRNAs to form slicer-independent effector complexes that bind target mRNAs and silence gene expression through translational repression and deadenylation but not cleavage. Here, we report that recombinant AGO3 loaded with miR-20a cleaves complementary target RNAs, whereas AGO3 loaded with let-7a, miR-19b or miR-16 does not, indicating that AGO3 has slicer activity but that this activity depends on the guide RNA. Our cleavage assays using chimeric guides revealed the significance of seed sequence for AGO3 activity, which depends specifically on the sequence of the post-seed. Unlike AGO2, target cleavage by AGO3 requires both 5'- and 3'-flanking regions. Our 3.28 A crystal structure shows that AGO3 forms a complete active site mirroring that of AGO2, but not a well-defined nucleic acid-binding channel. These results demonstrating that AGO3 also has slicer activity but with more intricate substrate requirements, explain the observation that AGO3 has retained the necessary catalytic residues throughout its evolution. In addition, our structure inspires the idea that the substrate-binding channel of AGO3 and consequently its cellular function, may be modulated by accessory proteins.
Human Argonaute3 has slicer activity.,Park MS, Phan HD, Busch F, Hinckley SH, Brackbill JA, Wysocki VH, Nakanishi K Nucleic Acids Res. 2017 Oct 11. doi: 10.1093/nar/gkx916. PMID:29040713[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ Hu Q, Tanasa B, Trabucchi M, Li W, Zhang J, Ohgi KA, Rose DW, Glass CK, Rosenfeld MG. DICER- and AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human stem cell proliferation. Nat Struct Mol Biol. 2012 Nov;19(11):1168-75. doi: 10.1038/nsmb.2400. Epub 2012, Oct 14. PMID:23064648 doi:http://dx.doi.org/10.1038/nsmb.2400
- ↑ Park MS, Phan HD, Busch F, Hinckley SH, Brackbill JA, Wysocki VH, Nakanishi K. Human Argonaute3 has slicer activity. Nucleic Acids Res. 2017 Oct 11. doi: 10.1093/nar/gkx916. PMID:29040713 doi:http://dx.doi.org/10.1093/nar/gkx916
|
