4cqo
From Proteopedia
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==Structure of the human CNOT1 superfamily homology domain in complex with a Nanos1 peptide== | ==Structure of the human CNOT1 superfamily homology domain in complex with a Nanos1 peptide== | ||
| - | <StructureSection load='4cqo' size='340' side='right' caption='[[4cqo]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='4cqo' size='340' side='right'caption='[[4cqo]], [[Resolution|resolution]] 2.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | [[4cqo]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CQO OCA]. | + | <table><tr><td colspan='2'>[[4cqo]] 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=4CQO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CQO FirstGlance]. <br> |
| - | <b> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| - | <b>Resources:</b> <span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4cqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cqo OCA], [https://pdbe.org/4cqo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cqo RCSB], [https://www.ebi.ac.uk/pdbsum/4cqo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cqo ProSAT]</span></td></tr> |
| - | + | </table> | |
| - | [ | + | |
== Function == | == Function == | ||
| - | [ | + | [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;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
The RNA-binding proteins of the Nanos family play an essential role in germ cell development and survival in a wide range of metazoan species. They function by suppressing the expression of target mRNAs through the recruitment of effector complexes, which include the CCR4-NOT deadenylase complex. Here, we show that the three human Nanos paralogs (Nanos1-3) interact with the CNOT1 C-terminal domain and determine the structural basis for the specific molecular recognition. Nanos1-3 bind CNOT1 through a short CNOT1-interacting motif (NIM) that is conserved in all vertebrates and some invertebrate species. The crystal structure of the human Nanos1 NIM peptide bound to CNOT1 reveals that the peptide opens a conserved hydrophobic pocket on the CNOT1 surface by inserting conserved aromatic residues. The substitutions of these aromatic residues in the Nanos1-3 NIMs abolish binding to CNOT1 and abrogate the ability of the proteins to repress translation. Our findings provide the structural basis for the recruitment of the CCR4-NOT complex by vertebrate Nanos, indicate that the NIMs are the major determinants of the translational repression mediated by Nanos, and identify the CCR4-NOT complex as the main effector complex for Nanos function. | The RNA-binding proteins of the Nanos family play an essential role in germ cell development and survival in a wide range of metazoan species. They function by suppressing the expression of target mRNAs through the recruitment of effector complexes, which include the CCR4-NOT deadenylase complex. Here, we show that the three human Nanos paralogs (Nanos1-3) interact with the CNOT1 C-terminal domain and determine the structural basis for the specific molecular recognition. Nanos1-3 bind CNOT1 through a short CNOT1-interacting motif (NIM) that is conserved in all vertebrates and some invertebrate species. The crystal structure of the human Nanos1 NIM peptide bound to CNOT1 reveals that the peptide opens a conserved hydrophobic pocket on the CNOT1 surface by inserting conserved aromatic residues. The substitutions of these aromatic residues in the Nanos1-3 NIMs abolish binding to CNOT1 and abrogate the ability of the proteins to repress translation. Our findings provide the structural basis for the recruitment of the CCR4-NOT complex by vertebrate Nanos, indicate that the NIMs are the major determinants of the translational repression mediated by Nanos, and identify the CCR4-NOT complex as the main effector complex for Nanos function. | ||
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Structural basis for the Nanos-mediated recruitment of the CCR4-NOT complex and translational repression.,Bhandari D, Raisch T, Weichenrieder O, Jonas S, Izaurralde E Genes Dev. 2014 Apr 15;28(8):888-901. doi: 10.1101/gad.237289.113. PMID:24736845<ref>PMID:24736845</ref> | Structural basis for the Nanos-mediated recruitment of the CCR4-NOT complex and translational repression.,Bhandari D, Raisch T, Weichenrieder O, Jonas S, Izaurralde E Genes Dev. 2014 Apr 15;28(8):888-901. doi: 10.1101/gad.237289.113. PMID:24736845<ref>PMID:24736845</ref> | ||
| - | From | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> | ||
| + | <div class="pdbe-citations 4cqo" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Bhandari D]] |
| - | [[Category: | + | [[Category: Izaurralde E]] |
| - | [[Category: | + | [[Category: Jonas S]] |
| - | [[Category: | + | [[Category: Raisch T]] |
| - | [[Category: | + | [[Category: Weichenrieder O]] |
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Current revision
Structure of the human CNOT1 superfamily homology domain in complex with a Nanos1 peptide
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