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| ==Crystal structure of human CNOT1 MIF4G domain in complex with a TTP peptide== | | ==Crystal structure of human CNOT1 MIF4G domain in complex with a TTP peptide== |
| <StructureSection load='4j8s' size='340' side='right' caption='[[4j8s]], [[Resolution|resolution]] 1.55Å' scene=''> | | <StructureSection load='4j8s' size='340' side='right'caption='[[4j8s]], [[Resolution|resolution]] 1.55Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4j8s]] 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=4J8S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J8S FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4j8s]] 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=4J8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J8S FirstGlance]. <br> |
| </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AD-005, CDC39, CNOT1, KIAA1007, NOT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 1.55Å</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=4j8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j8s OCA], [http://pdbe.org/4j8s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4j8s RCSB], [http://www.ebi.ac.uk/pdbsum/4j8s PDBsum]</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=4j8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j8s OCA], [https://pdbe.org/4j8s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j8s RCSB], [https://www.ebi.ac.uk/pdbsum/4j8s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j8s 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/TTP_HUMAN TTP_HUMAN]] mRNA-binding protein involved in post-transcriptional regulation of AU-rich element (ARE)-containing mRNAs. Acts by specifically binding ARE-containing mRNAs and promoting their degradation. Plays a key role in the post-transcriptional regulation of tumor necrosis factor (TNF).<ref>PMID:15014438</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;">
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| == Publication Abstract from PubMed ==
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| Tristetraprolin (TTP) is an RNA-binding protein that controls the inflammatory response by limiting the expression of several proinflammatory cytokines. TTP post-transcriptionally represses gene expression by interacting with AU-rich elements (AREs) in 3' untranslated regions of target mRNAs and subsequently engenders their deadenylation and decay. TTP accomplishes these tasks, at least in part, by recruiting the multisubunit CCR4-NOT deadenylase complex to the mRNA. Here we identify an evolutionarily conserved C-terminal motif in human TTP that directly binds a central domain of CNOT1, a core subunit of the CCR4-NOT complex. A high-resolution crystal structure of the TTP-CNOT1 complex was determined, providing the first structural insight, to our knowledge, into an ARE-binding protein bound to the CCR4-NOT complex. Mutations at the CNOT1-TTP interface impair TTP-mediated deadenylation, demonstrating the significance of this interaction in TTP-mediated gene silencing.
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| Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin.,Fabian MR, Frank F, Rouya C, Siddiqui N, Lai WS, Karetnikov A, Blackshear PJ, Nagar B, Sonenberg N Nat Struct Mol Biol. 2013 Jun;20(6):735-9. doi: 10.1038/nsmb.2572. Epub 2013 May , 5. PMID:23644599<ref>PMID:23644599</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 4j8s" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Blackshear, P J]] | | [[Category: Large Structures]] |
| [[Category: Fabian, M R]] | | [[Category: Blackshear PJ]] |
| [[Category: Frank, F]] | | [[Category: Fabian MR]] |
| [[Category: Karetnikov, A]] | | [[Category: Frank F]] |
| [[Category: Lai, W S]] | | [[Category: Karetnikov A]] |
| [[Category: Nagar, B]] | | [[Category: Lai WS]] |
| [[Category: Rouya, C]] | | [[Category: Nagar B]] |
| [[Category: Siddiqui, N]] | | [[Category: Rouya C]] |
| [[Category: Sonenberg, N]] | | [[Category: Siddiqui N]] |
| [[Category: Cytosol]]
| | [[Category: Sonenberg N]] |
| [[Category: Mif4g]]
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| [[Category: Protein binding]]
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| [[Category: Protein-protein interaction]]
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| [[Category: Ttp]]
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