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| | ==CNOT1 MIF4G domain - DDX6 complex== | | ==CNOT1 MIF4G domain - DDX6 complex== |
| - | <StructureSection load='4ct4' size='340' side='right' caption='[[4ct4]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='4ct4' size='340' side='right'caption='[[4ct4]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ct4]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CT4 OCA]. <br> | + | <table><tr><td colspan='2'>[[4ct4]] is a 4 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=4CT4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CT4 FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><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]] 2.3Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ct5|4ct5]], [[4ct6|4ct6]], [[4ct7|4ct7]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </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=4ct4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ct4 OCA], [https://pdbe.org/4ct4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ct4 RCSB], [https://www.ebi.ac.uk/pdbsum/4ct4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ct4 ProSAT]</span></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ct4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ct4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ct4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ct4 PDBsum]</span></td></tr> | + | </table> |
| - | <table> | + | |
| - | == Disease ==
| + | |
| - | [[http://www.uniprot.org/uniprot/DDX6_HUMAN DDX6_HUMAN]] Note=A chromosomal aberration involving DDX6 may be a cause of hematopoietic tumors such as B-cell lymphomas. Translocation t(11;14)(q23;q32).
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| | == 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/DDX6_HUMAN DDX6_HUMAN]] In the process of mRNA degradation, may play a role in mRNA decapping. | + | [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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| | Structural and Biochemical Insights to the Role of the CCR4-NOT Complex and DDX6 ATPase in MicroRNA Repression.,Mathys H, Basquin J, Ozgur S, Czarnocki-Cieciura M, Bonneau F, Aartse A, Dziembowski A, Nowotny M, Conti E, Filipowicz W Mol Cell. 2014 Apr 22. pii: S1097-2765(14)00269-X. doi:, 10.1016/j.molcel.2014.03.036. PMID:24768538<ref>PMID:24768538</ref> | | Structural and Biochemical Insights to the Role of the CCR4-NOT Complex and DDX6 ATPase in MicroRNA Repression.,Mathys H, Basquin J, Ozgur S, Czarnocki-Cieciura M, Bonneau F, Aartse A, Dziembowski A, Nowotny M, Conti E, Filipowicz W Mol Cell. 2014 Apr 22. pii: S1097-2765(14)00269-X. doi:, 10.1016/j.molcel.2014.03.036. PMID:24768538<ref>PMID:24768538</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 4ct4" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Basquin, J.]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Conti, E.]] | + | [[Category: Large Structures]] |
| - | [[Category: Ozgur, S.]] | + | [[Category: Basquin J]] |
| - | [[Category: Deadenylation]] | + | [[Category: Conti E]] |
| - | [[Category: Rna binding protein]] | + | [[Category: Ozgur S]] |
| - | [[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
MicroRNAs (miRNAs) control gene expression by regulating mRNA translation and stability. The CCR4-NOT complex is a key effector of miRNA function acting downstream of GW182/TNRC6 proteins. We show that miRNA-mediated repression requires the central region of CNOT1, the scaffold protein of CCR4-NOT. A CNOT1 domain interacts with CNOT9, which in turn interacts with the silencing domain of TNRC6 in a tryptophan motif-dependent manner. These interactions are direct, as shown by the structure of a CNOT9-CNOT1 complex with bound tryptophan. Another domain of CNOT1 with an MIF4G fold recruits the DEAD-box ATPase DDX6, a known translational inhibitor. Structural and biochemical approaches revealed that CNOT1 modulates the conformation of DDX6 and stimulates ATPase activity. Structure-based mutations showed that the CNOT1 MIF4G-DDX6 interaction is important for miRNA-mediated repression. These findings provide insights into the repressive steps downstream of the GW182/TNRC6 proteins and the role of the CCR4-NOT complex in posttranscriptional regulation in general.
Structural and Biochemical Insights to the Role of the CCR4-NOT Complex and DDX6 ATPase in MicroRNA Repression.,Mathys H, Basquin J, Ozgur S, Czarnocki-Cieciura M, Bonneau F, Aartse A, Dziembowski A, Nowotny M, Conti E, Filipowicz W Mol Cell. 2014 Apr 22. pii: S1097-2765(14)00269-X. doi:, 10.1016/j.molcel.2014.03.036. PMID:24768538[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
- ↑ Mathys H, Basquin J, Ozgur S, Czarnocki-Cieciura M, Bonneau F, Aartse A, Dziembowski A, Nowotny M, Conti E, Filipowicz W. Structural and Biochemical Insights to the Role of the CCR4-NOT Complex and DDX6 ATPase in MicroRNA Repression. Mol Cell. 2014 Apr 22. pii: S1097-2765(14)00269-X. doi:, 10.1016/j.molcel.2014.03.036. PMID:24768538 doi:http://dx.doi.org/10.1016/j.molcel.2014.03.036
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