6n4o
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
<StructureSection load='6n4o' size='340' side='right'caption='[[6n4o]], [[Resolution|resolution]] 2.90Å' scene=''> | <StructureSection load='6n4o' size='340' side='right'caption='[[6n4o]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6n4o]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N4O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N4O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n4o]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N4O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N4O FirstGlance]. <br> |
| - | </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=6n4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n4o OCA], [http://pdbe.org/6n4o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n4o RCSB], [http://www.ebi.ac.uk/pdbsum/6n4o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n4o ProSAT]</span></td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AGO2, EIF2C2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6n4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n4o OCA], [http://pdbe.org/6n4o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n4o RCSB], [http://www.ebi.ac.uk/pdbsum/6n4o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n4o ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| Line 12: | Line 13: | ||
microRNAs (miRNAs) guide Argonaute proteins to mRNAs targeted for repression. Target recognition occurs primarily through the miRNA seed region, composed of guide (g) nucleotides g2-g8. However, nucleotides beyond the seed are also important for some known miRNA-target interactions. Here, we report the structure of human Argonaute2 (Ago2) engaged with a target RNA recognized through both miRNA seed and supplementary (g13-g16) regions. Ago2 creates a "supplementary chamber" that accommodates up to five miRNA-target base pairs. Seed and supplementary chambers are adjacent to each other and can be bridged by an unstructured target loop of 1-15 nucleotides. Opening of the supplementary chamber may be constrained by tension in the miRNA 3' tail, as increases in miRNA length stabilize supplementary interactions. Contrary to previous reports, we demonstrate that optimal supplementary interactions can increase target affinity > 20-fold. These results provide a mechanism for extended miRNA targeting, suggest a function for 3' isomiRs in tuning miRNA targeting specificity, and indicate that supplementary interactions may contribute more to target recognition than is widely appreciated. | microRNAs (miRNAs) guide Argonaute proteins to mRNAs targeted for repression. Target recognition occurs primarily through the miRNA seed region, composed of guide (g) nucleotides g2-g8. However, nucleotides beyond the seed are also important for some known miRNA-target interactions. Here, we report the structure of human Argonaute2 (Ago2) engaged with a target RNA recognized through both miRNA seed and supplementary (g13-g16) regions. Ago2 creates a "supplementary chamber" that accommodates up to five miRNA-target base pairs. Seed and supplementary chambers are adjacent to each other and can be bridged by an unstructured target loop of 1-15 nucleotides. Opening of the supplementary chamber may be constrained by tension in the miRNA 3' tail, as increases in miRNA length stabilize supplementary interactions. Contrary to previous reports, we demonstrate that optimal supplementary interactions can increase target affinity > 20-fold. These results provide a mechanism for extended miRNA targeting, suggest a function for 3' isomiRs in tuning miRNA targeting specificity, and indicate that supplementary interactions may contribute more to target recognition than is widely appreciated. | ||
| - | Beyond the seed: structural basis for supplementary microRNA targeting by human Argonaute2.,Sheu-Gruttadauria J, Xiao Y, Gebert LF, MacRae IJ EMBO J. 2019 | + | Beyond the seed: structural basis for supplementary microRNA targeting by human Argonaute2.,Sheu-Gruttadauria J, Xiao Y, Gebert LF, MacRae IJ EMBO J. 2019 Jul 1;38(13):e101153. doi: 10.15252/embj.2018101153. Epub 2019 Apr, 26. PMID:31268608<ref>PMID:31268608</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 6n4o" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6n4o" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: MacRae, I J]] | [[Category: MacRae, I J]] | ||
Revision as of 07:58, 23 October 2019
Human Argonaute2-miR-122 bound to a seed and supplementary paired target
| |||||||||||
