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| | ==Complex of human CNOT9 and CNOT1 including one tryptophan== | | ==Complex of human CNOT9 and CNOT1 including one tryptophan== |
| - | <StructureSection load='4cru' size='340' side='right' caption='[[4cru]], [[Resolution|resolution]] 1.65Å' scene=''> | + | <StructureSection load='4cru' size='340' side='right'caption='[[4cru]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4cru]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CRU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CRU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4cru]] 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=4CRU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CRU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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]] 1.65Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4crv|4crv]], [[2fv2|2fv2]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=4cru FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cru OCA], [http://pdbe.org/4cru PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cru RCSB], [http://www.ebi.ac.uk/pdbsum/4cru PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cru 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=4cru FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cru OCA], [https://pdbe.org/4cru PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cru RCSB], [https://www.ebi.ac.uk/pdbsum/4cru PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cru ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CNOT1_HUMAN CNOT1_HUMAN]] Belongs to the CCR4-NOT complex that functions as general transcription regulation complex. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors.<ref>PMID:10637334</ref> <ref>PMID:16778766</ref> [[http://www.uniprot.org/uniprot/RCD1_HUMAN RCD1_HUMAN]] Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Involved in down-regulation of MYB- and JUN-dependent transcription. May play a role in cell differentiation (By similarity). Can bind oligonucleotides, such as poly-G, poly-C or poly-T (in vitro), but the physiological relevance of this is not certain. Does not bind poly-A. Enhances ligand-dependent transcriptional activity of nuclear hormone receptors, including RARA, expect ESR1-mediated transcription that is not only slightly increased, if at all.<ref>PMID:18180299</ref> <ref>PMID:17189474</ref> | + | [https://www.uniprot.org/uniprot/CNOT1_HUMAN CNOT1_HUMAN] Belongs to the CCR4-NOT complex that functions as general transcription regulation complex. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors.<ref>PMID:10637334</ref> <ref>PMID:16778766</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Boland, A]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chen, Y]] | + | [[Category: Large Structures]] |
| - | [[Category: Izaurralde, E]] | + | [[Category: Boland A]] |
| - | [[Category: Weichenrieder, O]] | + | [[Category: Chen Y]] |
| - | [[Category: Argonaute]] | + | [[Category: Izaurralde E]] |
| - | [[Category: Gene regulation]] | + | [[Category: Weichenrieder O]] |
| - | [[Category: Mirisc]]
| + | |
| - | [[Category: Mrna deadenylation]]
| + | |
| - | [[Category: Mrna silencing]]
| + | |
| - | [[Category: Tnrc6 binding]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
CNOT1_HUMAN Belongs to the CCR4-NOT complex that functions as general transcription regulation complex. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors.[1] [2]
Publication Abstract from PubMed
CCR4-NOT is a major effector complex in miRNA-mediated gene silencing. It is recruited to miRNA targets through interactions with tryptophan (W)-containing motifs in TNRC6/GW182 proteins and is required for both translational repression and degradation of miRNA targets. Here, we elucidate the structural basis for the repressive activity of CCR4-NOT and its interaction with TNRC6/GW182s. We show that the conserved CNOT9 subunit attaches to a domain of unknown function (DUF3819) in the CNOT1 scaffold. The resulting complex provides binding sites for TNRC6/GW182, and its crystal structure reveals tandem W-binding pockets located in CNOT9. We further show that the CNOT1 MIF4G domain interacts with the C-terminal RecA domain of DDX6, a translational repressor and decapping activator. The crystal structure of this complex demonstrates striking similarity to the eIF4G-eIF4A complex. Together, our data provide the missing physical links in a molecular pathway that connects miRNA target recognition with translational repression, deadenylation, and decapping.
A DDX6-CNOT1 Complex and W-Binding Pockets in CNOT9 Reveal Direct Links between miRNA Target Recognition and Silencing.,Chen Y, Boland A, Kuzuoglu-Ozturk D, Bawankar P, Loh B, Chang CT, Weichenrieder O, Izaurralde E Mol Cell. 2014 Apr 22. pii: S1097-2765(14)00267-6. doi:, 10.1016/j.molcel.2014.03.034. PMID:24768540[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Albert TK, Lemaire M, van Berkum NL, Gentz R, Collart MA, Timmers HT. Isolation and characterization of human orthologs of yeast CCR4-NOT complex subunits. Nucleic Acids Res. 2000 Feb 1;28(3):809-17. PMID:10637334
- ↑ Winkler GS, Mulder KW, Bardwell VJ, Kalkhoven E, Timmers HT. Human Ccr4-Not complex is a ligand-dependent repressor of nuclear receptor-mediated transcription. EMBO J. 2006 Jul 12;25(13):3089-99. Epub 2006 Jun 15. PMID:16778766 doi:7601194
- ↑ Chen Y, Boland A, Kuzuoglu-Ozturk D, Bawankar P, Loh B, Chang CT, Weichenrieder O, Izaurralde E. A DDX6-CNOT1 Complex and W-Binding Pockets in CNOT9 Reveal Direct Links between miRNA Target Recognition and Silencing. Mol Cell. 2014 Apr 22. pii: S1097-2765(14)00267-6. doi:, 10.1016/j.molcel.2014.03.034. PMID:24768540 doi:http://dx.doi.org/10.1016/j.molcel.2014.03.034
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