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| | ==Drosophila Bag-of-marbles CBM peptide bound to human CAF40== | | ==Drosophila Bag-of-marbles CBM peptide bound to human CAF40== |
| - | <StructureSection load='5onb' size='340' side='right' caption='[[5onb]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='5onb' size='340' side='right'caption='[[5onb]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5onb]] is a 8 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=5ONB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ONB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5onb]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ONB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ONB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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]] 3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CNOT9, RCD1, RQCD1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=5onb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5onb OCA], [http://pdbe.org/5onb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5onb RCSB], [http://www.ebi.ac.uk/pdbsum/5onb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5onb 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=5onb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5onb OCA], [https://pdbe.org/5onb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5onb RCSB], [https://www.ebi.ac.uk/pdbsum/5onb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5onb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CNOT9_HUMAN CNOT9_HUMAN]] Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Involved in down-regulation of MYB- and JUN-dependent transcription. May play a role in cell differentiation (By similarity). Can bind oligonucleotides, such as poly-G, poly-C or poly-T (in vitro), but the physiological relevance of this is not certain. Does not bind poly-A. Enhances ligand-dependent transcriptional activity of nuclear hormone receptors, including RARA, expect ESR1-mediated transcription that is not only slightly increased, if at all.<ref>PMID:17189474</ref> <ref>PMID:18180299</ref> [[http://www.uniprot.org/uniprot/BAM_DROME BAM_DROME]] Required to initiate both male and female gametogenesis. May regulate cystoblast cell divisions.<ref>PMID:2279698</ref> | + | [https://www.uniprot.org/uniprot/CNOT9_HUMAN CNOT9_HUMAN] Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Involved in down-regulation of MYB- and JUN-dependent transcription. May play a role in cell differentiation (By similarity). Can bind oligonucleotides, such as poly-G, poly-C or poly-T (in vitro), but the physiological relevance of this is not certain. Does not bind poly-A. Enhances ligand-dependent transcriptional activity of nuclear hormone receptors, including RARA, expect ESR1-mediated transcription that is not only slightly increased, if at all.<ref>PMID:17189474</ref> <ref>PMID:18180299</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Drosophila melanogaster]] |
| - | [[Category: Backhaus, C]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Izaurralde, E]] | + | [[Category: Large Structures]] |
| - | [[Category: Raisch, T]] | + | [[Category: Backhaus C]] |
| - | [[Category: Sgromo, A]] | + | [[Category: Izaurralde E]] |
| - | [[Category: Weichenrieder, O]] | + | [[Category: Raisch T]] |
| - | [[Category: Ccr4-not]] | + | [[Category: Sgromo A]] |
| - | [[Category: Deadenylation]] | + | [[Category: Weichenrieder O]] |
| - | [[Category: Gene regulation]]
| + | |
| - | [[Category: Translation]]
| + | |
| - | [[Category: Translational repression]]
| + | |
| Structural highlights
Function
CNOT9_HUMAN Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Involved in down-regulation of MYB- and JUN-dependent transcription. May play a role in cell differentiation (By similarity). Can bind oligonucleotides, such as poly-G, poly-C or poly-T (in vitro), but the physiological relevance of this is not certain. Does not bind poly-A. Enhances ligand-dependent transcriptional activity of nuclear hormone receptors, including RARA, expect ESR1-mediated transcription that is not only slightly increased, if at all.[1] [2]
Publication Abstract from PubMed
Drosophila melanogaster Bag-of-marbles (Bam) promotes germline stem cell (GSC) differentiation by repressing the expression of mRNAs encoding stem cell maintenance factors. Bam interacts with Benign gonial cell neoplasm (Bgcn) and the CCR4 deadenylase, a catalytic subunit of the CCR4-NOT complex. Bam has been proposed to bind CCR4 and displace it from the CCR4-NOT complex. Here, we investigated the interaction of Bam with the CCR4-NOT complex by using purified recombinant proteins. Unexpectedly, we found that Bam does not interact with CCR4 directly but instead binds to the CAF40 subunit of the complex in a manner mediated by a conserved N-terminal CAF40-binding motif (CBM). The crystal structure of the Bam CBM bound to CAF40 reveals that the CBM peptide adopts an alpha-helical conformation after binding to the concave surface of the crescent-shaped CAF40 protein. We further show that Bam-mediated mRNA decay and translational repression depend entirely on Bam's interaction with CAF40. Thus, Bam regulates the expression of its mRNA targets by recruiting the CCR4-NOT complex through interaction with CAF40.
Drosophila Bag-of-marbles directly interacts with the CAF40 subunit of the CCR4-NOT complex to elicit repression of mRNA targets.,Sgromo A, Raisch T, Backhaus C, Keskeny C, Alva V, Weichenrieder O, Izaurralde E RNA. 2017 Dec 18. pii: rna.064584.117. doi: 10.1261/rna.064584.117. PMID:29255063[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Garces RG, Gillon W, Pai EF. Atomic model of human Rcd-1 reveals an armadillo-like-repeat protein with in vitro nucleic acid binding properties. Protein Sci. 2007 Feb;16(2):176-88. Epub 2006 Dec 22. PMID:17189474 doi:10.1110/ps.062600507
- ↑ Garapaty S, Mahajan MA, Samuels HH. Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1. J Biol Chem. 2008 Mar 14;283(11):6806-16. doi: 10.1074/jbc.M706986200. Epub 2008 , Jan 7. PMID:18180299 doi:http://dx.doi.org/10.1074/jbc.M706986200
- ↑ Sgromo A, Raisch T, Backhaus C, Keskeny C, Alva V, Weichenrieder O, Izaurralde E. Drosophila Bag-of-marbles directly interacts with the CAF40 subunit of the CCR4-NOT complex to elicit repression of mRNA targets. RNA. 2017 Dec 18. pii: rna.064584.117. doi: 10.1261/rna.064584.117. PMID:29255063 doi:http://dx.doi.org/10.1261/rna.064584.117
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