|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Structure of the NOT-box domain of human CNOT3== | | ==Structure of the NOT-box domain of human CNOT3== |
| - | <StructureSection load='4c0g' size='340' side='right' caption='[[4c0g]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='4c0g' size='340' side='right'caption='[[4c0g]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4c0g]] is a 6 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=4C0G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C0G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4c0g]] is a 6 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=4C0G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C0G FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c0d|4c0d]], [[4c0f|4c0f]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4c0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c0g OCA], [http://pdbe.org/4c0g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c0g RCSB], [http://www.ebi.ac.uk/pdbsum/4c0g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c0g 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=4c0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c0g OCA], [https://pdbe.org/4c0g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c0g RCSB], [https://www.ebi.ac.uk/pdbsum/4c0g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c0g ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CNOT3_HUMAN CNOT3_HUMAN]] Precursor T-cell acute lymphoblastic leukemia. | + | [https://www.uniprot.org/uniprot/CNOT3_HUMAN CNOT3_HUMAN] Precursor T-cell acute lymphoblastic leukemia. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CNOT3_HUMAN CNOT3_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. May be involved in metabolic regulation; may be involved in recruitment of the CCR4-NOT complex to deadenylation target mRNAs involved in energy metabolism. Involved in mitotic progression and regulation of the spindle assembly checkpoint by regulating the stability of MAD1L1 mRNA. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may involve histone deacetylases. Involved in the maintenance of emryonic stem (ES) cell identity.<ref>PMID:14707134</ref> <ref>PMID:22342980</ref> <ref>PMID:22367759</ref> | + | [https://www.uniprot.org/uniprot/CNOT3_HUMAN CNOT3_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. May be involved in metabolic regulation; may be involved in recruitment of the CCR4-NOT complex to deadenylation target mRNAs involved in energy metabolism. Involved in mitotic progression and regulation of the spindle assembly checkpoint by regulating the stability of MAD1L1 mRNA. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may involve histone deacetylases. Involved in the maintenance of emryonic stem (ES) cell identity.<ref>PMID:14707134</ref> <ref>PMID:22342980</ref> <ref>PMID:22367759</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 25: |
Line 25: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Boland, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, Y]] | + | [[Category: Boland A]] |
| - | [[Category: Izaurralde, E]] | + | [[Category: Chen Y]] |
| - | [[Category: Jonas, S]] | + | [[Category: Izaurralde E]] |
| - | [[Category: Raisch, T]] | + | [[Category: Jonas S]] |
| - | [[Category: Weichenrieder, O]] | + | [[Category: Raisch T]] |
| - | [[Category: Ccr4-not]]
| + | [[Category: Weichenrieder O]] |
| - | [[Category: Deadenylation]]
| + | |
| - | [[Category: Gene regulation]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Mrna decay]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Disease
CNOT3_HUMAN Precursor T-cell acute lymphoblastic leukemia.
Function
CNOT3_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. May be involved in metabolic regulation; may be involved in recruitment of the CCR4-NOT complex to deadenylation target mRNAs involved in energy metabolism. Involved in mitotic progression and regulation of the spindle assembly checkpoint by regulating the stability of MAD1L1 mRNA. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may involve histone deacetylases. Involved in the maintenance of emryonic stem (ES) cell identity.[1] [2] [3]
Publication Abstract from PubMed
The CCR4-NOT deadenylase complex is a master regulator of translation and mRNA stability. Its NOT module orchestrates recruitment of the catalytic subunits to target mRNAs. We report the crystal structure of the human NOT module formed by the CNOT1, CNOT2 and CNOT3 C-terminal (-C) regions. CNOT1-C provides a rigid scaffold consisting of two perpendicular stacks of HEAT-like repeats. CNOT2-C and CNOT3-C heterodimerize through their SH3-like NOT-box domains. The heterodimer is stabilized and tightly anchored to the surface of CNOT1 through an unexpected intertwined arrangement of peptide regions lacking defined secondary structure. These assembly peptides mold onto their respective binding surfaces and form extensive interfaces. Mutagenesis of individual interfaces and perturbation of endogenous protein ratios cause defects in complex assembly and mRNA decay. Our studies provide a structural framework for understanding the recruitment of the CCR4-NOT complex to mRNA targets.
Structure and assembly of the NOT module of the human CCR4-NOT complex.,Boland A, Chen Y, Raisch T, Jonas S, Kuzuoglu-Ozturk D, Wohlbold L, Weichenrieder O, Izaurralde E Nat Struct Mol Biol. 2013 Oct 13. doi: 10.1038/nsmb.2681. PMID:24121232[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zwartjes CG, Jayne S, van den Berg DL, Timmers HT. Repression of promoter activity by CNOT2, a subunit of the transcription regulatory Ccr4-not complex. J Biol Chem. 2004 Mar 19;279(12):10848-54. Epub 2004 Jan 5. PMID:14707134 doi:http://dx.doi.org/10.1074/jbc.M311747200
- ↑ Takahashi A, Kikuguchi C, Morita M, Shimodaira T, Tokai-Nishizumi N, Yokoyama K, Ohsugi M, Suzuki T, Yamamoto T. Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression. Biochem Biophys Res Commun. 2012 Mar 9;419(2):268-73. doi:, 10.1016/j.bbrc.2012.02.007. Epub 2012 Feb 10. PMID:22342980 doi:http://dx.doi.org/10.1016/j.bbrc.2012.02.007
- ↑ Zheng X, Dumitru R, Lackford BL, Freudenberg JM, Singh AP, Archer TK, Jothi R, Hu G. Cnot1, Cnot2, and Cnot3 maintain mouse and human ESC identity and inhibit extraembryonic differentiation. Stem Cells. 2012 May;30(5):910-22. doi: 10.1002/stem.1070. PMID:22367759 doi:http://dx.doi.org/10.1002/stem.1070
- ↑ Boland A, Chen Y, Raisch T, Jonas S, Kuzuoglu-Ozturk D, Wohlbold L, Weichenrieder O, Izaurralde E. Structure and assembly of the NOT module of the human CCR4-NOT complex. Nat Struct Mol Biol. 2013 Oct 13. doi: 10.1038/nsmb.2681. PMID:24121232 doi:http://dx.doi.org/10.1038/nsmb.2681
|
