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| | ==Solution structure of CPEB1 ZZ domain in the free state== | | ==Solution structure of CPEB1 ZZ domain in the free state== |
| - | <StructureSection load='2mke' size='340' side='right' caption='[[2mke]], [[NMR_Ensembles_of_Models | 26 NMR models]]' scene=''> | + | <StructureSection load='2mke' size='340' side='right'caption='[[2mke]], [[NMR_Ensembles_of_Models | 26 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mke]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MKE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MKE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mke]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MKE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MKE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2mkh|2mkh]], [[2mki|2mki]], [[2mkj|2mkj]], [[2mkk|2mkk]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2mkh|2mkh]], [[2mki|2mki]], [[2mkj|2mkj]], [[2mkk|2mkk]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CPEB1, CPEB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CPEB1, CPEB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2mke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mke OCA], [http://pdbe.org/2mke PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mke RCSB], [http://www.ebi.ac.uk/pdbsum/2mke PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mke 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=2mke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mke OCA], [https://pdbe.org/2mke PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mke RCSB], [https://www.ebi.ac.uk/pdbsum/2mke PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mke ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CPEB1_HUMAN CPEB1_HUMAN]] Sequence-specific RNA-binding protein that regulates mRNA cytoplasmic polyadenylation and translation initiation during oocyte maturation, early development and at postsynapse sites of neurons. Binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR. In absence of phosphorylation and in association with TACC3 is also involved as a repressor of translation of CPE-containing mRNA; a repression that is relieved by phosphorylation or degradation (By similarity). Involved in the transport of CPE-containing mRNA to dendrites; those mRNAs may be transported to dendrites in a translationally dormant form and translationally activated at synapses (By similarity). Its interaction with APLP1 promotes local CPE-containing mRNA polyadenylation and translation activation (By similarity). Induces the assembly of stress granules in the absence of stress.<ref>PMID:15966895</ref> <ref>PMID:15731006</ref> | + | [[https://www.uniprot.org/uniprot/CPEB1_HUMAN CPEB1_HUMAN]] Sequence-specific RNA-binding protein that regulates mRNA cytoplasmic polyadenylation and translation initiation during oocyte maturation, early development and at postsynapse sites of neurons. Binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR. In absence of phosphorylation and in association with TACC3 is also involved as a repressor of translation of CPE-containing mRNA; a repression that is relieved by phosphorylation or degradation (By similarity). Involved in the transport of CPE-containing mRNA to dendrites; those mRNAs may be transported to dendrites in a translationally dormant form and translationally activated at synapses (By similarity). Its interaction with APLP1 promotes local CPE-containing mRNA polyadenylation and translation activation (By similarity). Induces the assembly of stress granules in the absence of stress.<ref>PMID:15966895</ref> <ref>PMID:15731006</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Afroz, T]] | | [[Category: Afroz, T]] |
| | [[Category: Allain, F H.T]] | | [[Category: Allain, F H.T]] |
| Structural highlights
Function
[CPEB1_HUMAN] Sequence-specific RNA-binding protein that regulates mRNA cytoplasmic polyadenylation and translation initiation during oocyte maturation, early development and at postsynapse sites of neurons. Binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR. In absence of phosphorylation and in association with TACC3 is also involved as a repressor of translation of CPE-containing mRNA; a repression that is relieved by phosphorylation or degradation (By similarity). Involved in the transport of CPE-containing mRNA to dendrites; those mRNAs may be transported to dendrites in a translationally dormant form and translationally activated at synapses (By similarity). Its interaction with APLP1 promotes local CPE-containing mRNA polyadenylation and translation activation (By similarity). Induces the assembly of stress granules in the absence of stress.[1] [2]
Publication Abstract from PubMed
Cytoplasmic changes in polyA tail length is a key mechanism of translational control and is implicated in germline development, synaptic plasticity, cellular proliferation, senescence, and cancer progression. The presence of a U-rich cytoplasmic polyadenylation element (CPE) in the 3' untranslated regions (UTRs) of the responding mRNAs gives them the selectivity to be regulated by the CPE-binding (CPEB) family of proteins, which recognizes RNA via the tandem RNA recognition motifs (RRMs). Here we report the solution structures of the tandem RRMs of two human paralogs (CPEB1 and CPEB4) in their free and RNA-bound states. The structures reveal an unprecedented arrangement of RRMs in the free state that undergo an original closure motion upon RNA binding that ensures high fidelity. Structural and functional characterization of the ZZ domain (zinc-binding domain) of CPEB1 suggests a role in both protein-protein and protein-RNA interactions. Together with functional studies, the structures reveal how RNA binding by CPEB proteins leads to an optimal positioning of the N-terminal and ZZ domains at the 3' UTR, which favors the nucleation of the functional ribonucleoprotein complexes for translation regulation.
A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins.,Afroz T, Skrisovska L, Belloc E, Guillen-Boixet J, Mendez R, Allain FH Genes Dev. 2014 Jul 1;28(13):1498-514. doi: 10.1101/gad.241133.114. PMID:24990967[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sasayama T, Marumoto T, Kunitoku N, Zhang D, Tamaki N, Kohmura E, Saya H, Hirota T. Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1. Genes Cells. 2005 Jul;10(7):627-38. PMID:15966895 doi:10.1111/j.1365-2443.2005.00870.x
- ↑ Wilczynska A, Aigueperse C, Kress M, Dautry F, Weil D. The translational regulator CPEB1 provides a link between dcp1 bodies and stress granules. J Cell Sci. 2005 Mar 1;118(Pt 5):981-92. PMID:15731006 doi:118/5/981
- ↑ Afroz T, Skrisovska L, Belloc E, Guillen-Boixet J, Mendez R, Allain FH. A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins. Genes Dev. 2014 Jul 1;28(13):1498-514. doi: 10.1101/gad.241133.114. PMID:24990967 doi:http://dx.doi.org/10.1101/gad.241133.114
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