6oon: Difference between revisions
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<StructureSection load='6oon' size='340' side='right'caption='[[6oon]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='6oon' size='340' side='right'caption='[[6oon]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6oon]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OON OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OON FirstGlance]. <br> | <table><tr><td colspan='2'>[[6oon]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OON OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OON 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=6oon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oon OCA], [http://pdbe.org/6oon PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oon RCSB], [http://www.ebi.ac.uk/pdbsum/6oon PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oon ProSAT]</span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AGO4, EIF2C4, KIAA1567 ([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=6oon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oon OCA], [http://pdbe.org/6oon PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oon RCSB], [http://www.ebi.ac.uk/pdbsum/6oon PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oon ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/AGO4_HUMAN AGO4_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. Also required for RNA-directed transcription and replication of the human hapatitis delta virus (HDV).[HAMAP-Rule:MF_03033]<ref>PMID:15337849</ref> <ref>PMID:18552826</ref> <ref>PMID:18771919</ref> | [[http://www.uniprot.org/uniprot/AGO4_HUMAN AGO4_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. Also required for RNA-directed transcription and replication of the human hapatitis delta virus (HDV).[HAMAP-Rule:MF_03033]<ref>PMID:15337849</ref> <ref>PMID:18552826</ref> <ref>PMID:18771919</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Despite the relevance of Argonaute proteins in RNA silencing, little is known about the structural steps of small RNA loading to form RNA-induced silencing complexes (RISCs). We report the 1.9 A crystal structure of human Argonaute4 with guide RNA. Comparison with the previously determined apo structure of Neurospora crassa QDE2 revealed that the PIWI domain has two subdomains. Binding of guide RNA fastens the subdomains, thereby rearranging the active-site residues and increasing the affinity for TNRC6 proteins. We also identified two water pockets beneath the nucleic acid-binding channel that appeared to stabilize the mature RISC. Indeed, mutating the water-pocket residues of Argonaute2 and Argonaute4 compromised RISC assembly. Simulations predict that internal water molecules are exchangeable with the bulk solvent but always occupy specific positions at the domain interfaces. These results suggest that after guide RNA-driven conformational changes, water-mediated hydrogen-bonding networks tie together the converged domains to complete the functional RISC structure. | |||
Multidomain Convergence of Argonaute during RISC Assembly Correlates with the Formation of Internal Water Clusters.,Park MS, Araya-Secchi R, Brackbill JA, Phan HD, Kehling AC, Abd El-Wahab EW, Dayeh DM, Sotomayor M, Nakanishi K Mol Cell. 2019 Aug 22;75(4):725-740.e6. doi: 10.1016/j.molcel.2019.06.011. Epub, 2019 Jul 16. PMID:31324450<ref>PMID:31324450</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6oon" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Brackbill, J A]] | [[Category: Brackbill, J A]] | ||
Revision as of 14:46, 13 November 2019
RNA-binding proteinRNA-binding protein
Structural highlights
Function[AGO4_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. Also required for RNA-directed transcription and replication of the human hapatitis delta virus (HDV).[HAMAP-Rule:MF_03033][1] [2] [3] Publication Abstract from PubMedDespite the relevance of Argonaute proteins in RNA silencing, little is known about the structural steps of small RNA loading to form RNA-induced silencing complexes (RISCs). We report the 1.9 A crystal structure of human Argonaute4 with guide RNA. Comparison with the previously determined apo structure of Neurospora crassa QDE2 revealed that the PIWI domain has two subdomains. Binding of guide RNA fastens the subdomains, thereby rearranging the active-site residues and increasing the affinity for TNRC6 proteins. We also identified two water pockets beneath the nucleic acid-binding channel that appeared to stabilize the mature RISC. Indeed, mutating the water-pocket residues of Argonaute2 and Argonaute4 compromised RISC assembly. Simulations predict that internal water molecules are exchangeable with the bulk solvent but always occupy specific positions at the domain interfaces. These results suggest that after guide RNA-driven conformational changes, water-mediated hydrogen-bonding networks tie together the converged domains to complete the functional RISC structure. Multidomain Convergence of Argonaute during RISC Assembly Correlates with the Formation of Internal Water Clusters.,Park MS, Araya-Secchi R, Brackbill JA, Phan HD, Kehling AC, Abd El-Wahab EW, Dayeh DM, Sotomayor M, Nakanishi K Mol Cell. 2019 Aug 22;75(4):725-740.e6. doi: 10.1016/j.molcel.2019.06.011. Epub, 2019 Jul 16. PMID:31324450[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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