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| | <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 == |
| - | <table><tr><td colspan='2'>[[4cqo]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CQO OCA]. <br> | + | <table><tr><td colspan='2'>[[4cqo]] is a 4 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=4CQO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CQO FirstGlance]. <br> |
| - | </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>
| + | </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=4cqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cqo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cqo RCSB], [http://www.ebi.ac.uk/pdbsum/4cqo PDBsum]</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=4cqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cqo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cqo RCSB], [http://www.ebi.ac.uk/pdbsum/4cqo PDBsum]</span></td></tr> | + | </table> |
| - | <table> | + | |
| | == Disease == | | == Disease == |
| | [[http://www.uniprot.org/uniprot/NANO1_HUMAN NANO1_HUMAN]] Male infertility due to NANOS1 mutation. The disease is caused by mutations affecting the gene represented in this entry. | | [[http://www.uniprot.org/uniprot/NANO1_HUMAN NANO1_HUMAN]] Male infertility due to NANOS1 mutation. The disease is caused by mutations affecting the gene represented in this entry. |
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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 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> |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bhandari, D.]] | + | [[Category: Human]] |
| - | [[Category: Izaurralde, E.]] | + | [[Category: Bhandari, D]] |
| - | [[Category: Jonas, S.]] | + | [[Category: Izaurralde, E]] |
| - | [[Category: Raisch, T.]] | + | [[Category: Jonas, S]] |
| - | [[Category: Weichenrieder, O.]] | + | [[Category: Raisch, T]] |
| | + | [[Category: Weichenrieder, O]] |
| | [[Category: Deadenylation]] | | [[Category: Deadenylation]] |
| | [[Category: Development]] | | [[Category: Development]] |
| Structural highlights
Disease
[NANO1_HUMAN] Male infertility due to NANOS1 mutation. The disease is caused by mutations affecting the gene represented in this entry.
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] [NANO1_HUMAN] May act as a translational repressor which regulates translation of specific mRNAs by forming a complex with PUM2 that associates with the 3'-UTR of mRNA targets. Capable of interfering with the proadhesive and anti-invasive functions of E-cadherin. Up-regulates the production of MMP14 to promote tumor cell invasion.[3] [4]
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.
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[5]
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
- ↑ Strumane K, Bonnomet A, Stove C, Vandenbroucke R, Nawrocki-Raby B, Bruyneel E, Mareel M, Birembaut P, Berx G, van Roy F. E-cadherin regulates human Nanos1, which interacts with p120ctn and induces tumor cell migration and invasion. Cancer Res. 2006 Oct 15;66(20):10007-15. PMID:17047063 doi:http://dx.doi.org/10.1158/0008-5472.CAN-05-3096
- ↑ Bonnomet A, Polette M, Strumane K, Gilles C, Dalstein V, Kileztky C, Berx G, van Roy F, Birembaut P, Nawrocki-Raby B. The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by upregulating MT1-MMP expression. Oncogene. 2008 Jun 12;27(26):3692-9. doi: 10.1038/sj.onc.1211035. Epub 2008 Jan, 28. PMID:18223680 doi:http://dx.doi.org/10.1038/sj.onc.1211035
- ↑ Bhandari D, Raisch T, Weichenrieder O, Jonas S, Izaurralde E. Structural basis for the Nanos-mediated recruitment of the CCR4-NOT complex and translational repression. Genes Dev. 2014 Apr 15;28(8):888-901. doi: 10.1101/gad.237289.113. PMID:24736845 doi:http://dx.doi.org/10.1101/gad.237289.113
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