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New page: left|200px<br /><applet load="2f8s" size="350" color="white" frame="true" align="right" spinBox="true" caption="2f8s, resolution 3.00Å" /> '''Crystal structure of...
 
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[[Image:2f8s.gif|left|200px]]<br /><applet load="2f8s" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2f8s, resolution 3.00&Aring;" />
'''Crystal structure of Aa-Ago with externally-bound siRNA'''<br />


==Overview==
==Crystal structure of Aa-Ago with externally-bound siRNA==
Argonaute proteins are key components of the RNA-induced silencing complex, (RISC). They provide both architectural and catalytic functionalities, associated with small interfering RNA (siRNA) guide strand recognition and, subsequent guide strand-mediated cleavage of complementary mRNAs. We, report on the 3.0 A crystal structures of 22-mer and 26-mer siRNAs bound, to Aquifex aeolicus Argonaute (Aa-Ago), where one 2 nt 3' overhang of the, siRNA inserts into a cavity positioned on the outer surface of the, PAZ-containing lobe of the bilobal Aa-Ago architecture. The first overhang, nucleotide stacks over a tyrosine ring, while the second overhang, nucleotide, together with the intervening sugar-phosphate backbone, inserts into a preformed surface cavity. Photochemical crosslinking, studies on Aa-Ago with 5-iodoU-labeled single-stranded siRNA and siRNA, duplex provide support for this externally bound siRNA-Aa-Ago complex. The, structure and biochemical data together provide insights into a, protein-RNA recognition event potentially associated with the RISC-loading, pathway.
<StructureSection load='2f8s' size='340' side='right'caption='[[2f8s]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2f8s]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus]. The February 2008 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Small Interfering RNA''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2008_2 10.2210/rcsb_pdb/mom_2008_2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F8S FirstGlance]. <br>
</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&#8491;</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=2f8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f8s OCA], [https://pdbe.org/2f8s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f8s RCSB], [https://www.ebi.ac.uk/pdbsum/2f8s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f8s ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O67434_AQUAE O67434_AQUAE]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f8/2f8s_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2f8s ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Argonaute proteins are key components of the RNA-induced silencing complex (RISC). They provide both architectural and catalytic functionalities associated with small interfering RNA (siRNA) guide strand recognition and subsequent guide strand-mediated cleavage of complementary mRNAs. We report on the 3.0 A crystal structures of 22-mer and 26-mer siRNAs bound to Aquifex aeolicus Argonaute (Aa-Ago), where one 2 nt 3' overhang of the siRNA inserts into a cavity positioned on the outer surface of the PAZ-containing lobe of the bilobal Aa-Ago architecture. The first overhang nucleotide stacks over a tyrosine ring, while the second overhang nucleotide, together with the intervening sugar-phosphate backbone, inserts into a preformed surface cavity. Photochemical crosslinking studies on Aa-Ago with 5-iodoU-labeled single-stranded siRNA and siRNA duplex provide support for this externally bound siRNA-Aa-Ago complex. The structure and biochemical data together provide insights into a protein-RNA recognition event potentially associated with the RISC-loading pathway.


==About this Structure==
A potential protein-RNA recognition event along the RISC-loading pathway from the structure of A. aeolicus Argonaute with externally bound siRNA.,Yuan YR, Pei Y, Chen HY, Tuschl T, Patel DJ Structure. 2006 Oct;14(10):1557-65. PMID:17027504<ref>PMID:17027504</ref>
2F8S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F8S OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
A potential protein-RNA recognition event along the RISC-loading pathway from the structure of A. aeolicus Argonaute with externally bound siRNA., Yuan YR, Pei Y, Chen HY, Tuschl T, Patel DJ, Structure. 2006 Oct;14(10):1557-65. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17027504 17027504]
</div>
<div class="pdbe-citations 2f8s" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Argonaute 3D structures|Argonaute 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aquifex aeolicus]]
[[Category: Aquifex aeolicus]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Chen, H.Y.]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Patel, D.J.]]
[[Category: Small Interfering RNA]]
[[Category: Yuan, Y.R.]]
[[Category: Chen HY]]
[[Category: argonaute]]
[[Category: Patel DJ]]
[[Category: risc loading complex]]
[[Category: Yuan YR]]
[[Category: sirna]]
 
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