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==Crystal structure of the PAZ domain of human eIF2c1 in complex with a 9-mer siRNA-like duplex of deoxynucleotide overhang==
==Crystal structure of the PAZ domain of human eIF2c1 in complex with a 9-mer siRNA-like duplex of deoxynucleotide overhang==
<StructureSection load='1si2' size='340' side='right' caption='[[1si2]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='1si2' size='340' side='right'caption='[[1si2]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1si2]] is a 2 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=1SI2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1SI2 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1si2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SI2 FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1si3|1si3]]</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]] 2.6&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF2C1 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=1si2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1si2 OCA], [https://pdbe.org/1si2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1si2 RCSB], [https://www.ebi.ac.uk/pdbsum/1si2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1si2 ProSAT]</span></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=1si2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1si2 OCA], [http://pdbe.org/1si2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1si2 RCSB], [http://www.ebi.ac.uk/pdbsum/1si2 PDBsum]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/AGO1_HUMAN 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).<ref>PMID:16289642</ref> <ref>PMID:16936728</ref> <ref>PMID:18771919</ref>
[https://www.uniprot.org/uniprot/AGO1_HUMAN 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).<ref>PMID:16289642</ref> <ref>PMID:16936728</ref> <ref>PMID:18771919</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/si/1si2_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/si/1si2_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
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</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=1si2 ConSurf].
</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=1si2 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Short RNAs mediate gene silencing, a process associated with virus resistance, developmental control and heterochromatin formation in eukaryotes. RNA silencing is initiated through Dicer-mediated processing of double-stranded RNA into small interfering RNA (siRNA). The siRNA guide strand associates with the Argonaute protein in silencing effector complexes, recognizes complementary sequences and targets them for silencing. The PAZ domain is an RNA-binding module found in Argonaute and some Dicer proteins and its structure has been determined in the free state. Here, we report the 2.6 A crystal structure of the PAZ domain from human Argonaute eIF2c1 bound to both ends of a 9-mer siRNA-like duplex. In a sequence-independent manner, PAZ anchors the 2-nucleotide 3' overhang of the siRNA-like duplex within a highly conserved binding pocket, and secures the duplex by binding the 7-nucleotide phosphodiester backbone of the overhang-containing strand and capping the 5'-terminal residue of the complementary strand. On the basis of the structure and on binding assays, we propose that PAZ might serve as an siRNA-end-binding module for siRNA transfer in the RNA silencing pathway, and as an anchoring site for the 3' end of guide RNA within silencing effector complexes.
Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain.,Ma JB, Ye K, Patel DJ Nature. 2004 May 20;429(6989):318-22. PMID:15152257<ref>PMID:15152257</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1si2" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Argonaute|Argonaute]]
*[[Argonaute 3D structures|Argonaute 3D structures]]
*[[Eukaryotic initiation factor|Eukaryotic initiation factor]]
*[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Ma, J B]]
[[Category: Large Structures]]
[[Category: Patel, D]]
[[Category: Ma JB]]
[[Category: Ye, K]]
[[Category: Patel D]]
[[Category: Double helix]]
[[Category: Ye K]]
[[Category: Gene regulation-rna-dna complex]]
[[Category: Overhang]]
[[Category: Protein-rna complex]]
[[Category: Rna interference]]

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