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| | ==Structural basis of EZH2 recognition by EED== | | ==Structural basis of EZH2 recognition by EED== |
| - | <StructureSection load='2qxv' size='340' side='right' caption='[[2qxv]], [[Resolution|resolution]] 1.82Å' scene=''> | + | <StructureSection load='2qxv' size='340' side='right'caption='[[2qxv]], [[Resolution|resolution]] 1.82Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qxv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QXV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QXV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qxv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QXV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QXV FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hEED ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Ezh2, Enx1h ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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]] 1.82Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </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=2qxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qxv OCA], [https://pdbe.org/2qxv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qxv RCSB], [https://www.ebi.ac.uk/pdbsum/2qxv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qxv ProSAT]</span></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=2qxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qxv OCA], [http://pdbe.org/2qxv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qxv RCSB], [http://www.ebi.ac.uk/pdbsum/2qxv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2qxv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/EED_MOUSE EED_MOUSE]] Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark (By similarity). The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (By similarity). Genes repressed by the PRC2/EED-EZH2 complex include HOXA7, HOXB6 and HOXC8. Plays a role in X chromosome inactivation (XCI), in which one of the two X chromosomes in female mammals is transcriptionally silenced to equalize X-linked gene dosage with XY males. Required for stable maintenance of XCI in both embryonic and extraembryonic tissues. May prevent transcriptional activation of facultative heterochromatin during differentiation. Required for development of secondary trophoblast giant cells during placental development. May regulate hippocampal synaptic plasticity in the developing brain.<ref>PMID:9234727</ref> <ref>PMID:9742080</ref> <ref>PMID:11479595</ref> <ref>PMID:12370779</ref> <ref>PMID:12689588</ref> <ref>PMID:12627233</ref> <ref>PMID:12649488</ref> <ref>PMID:15516932</ref> <ref>PMID:15916951</ref> <ref>PMID:16618801</ref> <ref>PMID:16415857</ref> <ref>PMID:17259173</ref> <ref>PMID:17997413</ref> <ref>PMID:18201968</ref> [[http://www.uniprot.org/uniprot/EZH2_MOUSE EZH2_MOUSE]] Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Compared to EZH2-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXA7, HOXB6 and HOXC8. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4.<ref>PMID:12689588</ref> <ref>PMID:15520282</ref> <ref>PMID:15516932</ref> <ref>PMID:19026780</ref> <ref>PMID:18086877</ref> | + | [https://www.uniprot.org/uniprot/EED_MOUSE EED_MOUSE] Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark (By similarity). The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (By similarity). Genes repressed by the PRC2/EED-EZH2 complex include HOXA7, HOXB6 and HOXC8. Plays a role in X chromosome inactivation (XCI), in which one of the two X chromosomes in female mammals is transcriptionally silenced to equalize X-linked gene dosage with XY males. Required for stable maintenance of XCI in both embryonic and extraembryonic tissues. May prevent transcriptional activation of facultative heterochromatin during differentiation. Required for development of secondary trophoblast giant cells during placental development. May regulate hippocampal synaptic plasticity in the developing brain.<ref>PMID:9234727</ref> <ref>PMID:9742080</ref> <ref>PMID:11479595</ref> <ref>PMID:12370779</ref> <ref>PMID:12689588</ref> <ref>PMID:12627233</ref> <ref>PMID:12649488</ref> <ref>PMID:15516932</ref> <ref>PMID:15916951</ref> <ref>PMID:16618801</ref> <ref>PMID:16415857</ref> <ref>PMID:17259173</ref> <ref>PMID:17997413</ref> <ref>PMID:18201968</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2qxv ConSurf]. | | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2qxv ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| - | <div style="background-color:#fffaf0;"> | |
| - | == Publication Abstract from PubMed == | |
| - | The WD-repeat domain is a highly conserved recognition module in eukaryotes involved in diverse cellular processes. It is still not well understood how the bottom of a WD-repeat domain recognizes its binding partners. The WD-repeat-containing protein EED is one component of the PRC2 complex that possesses histone methyltransferase activity required for gene repression. Here we report the crystal structure of EED in complex with a 30 residue peptide from EZH2. The structure reveals that the peptide binds to the bottom of the WD-repeat domain of EED. The structural determinants of EZH2-EED interaction are present not only in EZH2 and EZH1 but also in its Drosophila homolog E(Z), suggesting that the recognition of ESC by E(Z) in Drosophila employs similar structural motifs. Structure-based mutagenesis identified critical residues from both EED and EZH2 for their interaction. The structure presented here may provide a template for understanding of how WD-repeat proteins recognize their interacting proteins. | |
| - | | |
| - | Structural basis of EZH2 recognition by EED.,Han Z, Xing X, Hu M, Zhang Y, Liu P, Chai J Structure. 2007 Oct;15(10):1306-15. PMID:17937919<ref>PMID:17937919</ref> | |
| - | | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | </div> | |
| - | <div class="pdbe-citations 2qxv" style="background-color:#fffaf0;"></div> | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Histone-lysine N-methyltransferase]] | + | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Han, Z]] | + | [[Category: Han Z]] |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Gene regulation]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Polycomb repressive complex 2]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| - | [[Category: Wd-repeat domain]]
| + | |
| Structural highlights
Function
EED_MOUSE Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark (By similarity). The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (By similarity). Genes repressed by the PRC2/EED-EZH2 complex include HOXA7, HOXB6 and HOXC8. Plays a role in X chromosome inactivation (XCI), in which one of the two X chromosomes in female mammals is transcriptionally silenced to equalize X-linked gene dosage with XY males. Required for stable maintenance of XCI in both embryonic and extraembryonic tissues. May prevent transcriptional activation of facultative heterochromatin during differentiation. Required for development of secondary trophoblast giant cells during placental development. May regulate hippocampal synaptic plasticity in the developing brain.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Denisenko ON, Bomsztyk K. The product of the murine homolog of the Drosophila extra sex combs gene displays transcriptional repressor activity. Mol Cell Biol. 1997 Aug;17(8):4707-17. PMID:9234727
- ↑ Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K. Point mutations in the WD40 domain of Eed block its interaction with Ezh2. Mol Cell Biol. 1998 Oct;18(10):5634-42. PMID:9742080
- ↑ Wang J, Mager J, Chen Y, Schneider E, Cross JC, Nagy A, Magnuson T. Imprinted X inactivation maintained by a mouse Polycomb group gene. Nat Genet. 2001 Aug;28(4):371-5. PMID:11479595 doi:http://dx.doi.org/10.1038/ng574
- ↑ Wang J, Mager J, Schnedier E, Magnuson T. The mouse PcG gene eed is required for Hox gene repression and extraembryonic development. Mamm Genome. 2002 Sep;13(9):493-503. PMID:12370779 doi:http://dx.doi.org/10.1007/s00335-002-2182-7
- ↑ Silva J, Mak W, Zvetkova I, Appanah R, Nesterova TB, Webster Z, Peters AH, Jenuwein T, Otte AP, Brockdorff N. Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. Dev Cell. 2003 Apr;4(4):481-95. PMID:12689588
- ↑ Mager J, Montgomery ND, de Villena FP, Magnuson T. Genome imprinting regulated by the mouse Polycomb group protein Eed. Nat Genet. 2003 Apr;33(4):502-7. Epub 2003 Mar 10. PMID:12627233 doi:http://dx.doi.org/10.1038/ng1125
- ↑ Plath K, Fang J, Mlynarczyk-Evans SK, Cao R, Worringer KA, Wang H, de la Cruz CC, Otte AP, Panning B, Zhang Y. Role of histone H3 lysine 27 methylation in X inactivation. Science. 2003 Apr 4;300(5616):131-5. Epub 2003 Mar 20. PMID:12649488 doi:http://dx.doi.org/10.1126/science.1084274
- ↑ Umlauf D, Goto Y, Cao R, Cerqueira F, Wagschal A, Zhang Y, Feil R. Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes. Nat Genet. 2004 Dec;36(12):1296-300. Epub 2004 Oct 31. PMID:15516932 doi:http://dx.doi.org/ng1467
- ↑ Montgomery ND, Yee D, Chen A, Kalantry S, Chamberlain SJ, Otte AP, Magnuson T. The murine polycomb group protein Eed is required for global histone H3 lysine-27 methylation. Curr Biol. 2005 May 24;15(10):942-7. PMID:15916951 doi:http://dx.doi.org/10.1016/j.cub.2005.04.051
- ↑ Bracken AP, Dietrich N, Pasini D, Hansen KH, Helin K. Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev. 2006 May 1;20(9):1123-36. Epub 2006 Apr 17. PMID:16618801 doi:http://dx.doi.org/10.1101/gad.381706
- ↑ Kalantry S, Mills KC, Yee D, Otte AP, Panning B, Magnuson T. The Polycomb group protein Eed protects the inactive X-chromosome from differentiation-induced reactivation. Nat Cell Biol. 2006 Feb;8(2):195-202. Epub 2006 Jan 15. PMID:16415857 doi:http://dx.doi.org/10.1038/ncb1351
- ↑ Kim SY, Levenson JM, Korsmeyer S, Sweatt JD, Schumacher A. Developmental regulation of Eed complex composition governs a switch in global histone modification in brain. J Biol Chem. 2007 Mar 30;282(13):9962-72. Epub 2007 Jan 26. PMID:17259173 doi:http://dx.doi.org/10.1074/jbc.M608722200
- ↑ Montgomery ND, Yee D, Montgomery SA, Magnuson T. Molecular and functional mapping of EED motifs required for PRC2-dependent histone methylation. J Mol Biol. 2007 Dec 14;374(5):1145-57. Epub 2007 Oct 22. PMID:17997413 doi:http://dx.doi.org/10.1016/j.jmb.2007.10.040
- ↑ Ura H, Usuda M, Kinoshita K, Sun C, Mori K, Akagi T, Matsuda T, Koide H, Yokota T. STAT3 and Oct-3/4 control histone modification through induction of Eed in embryonic stem cells. J Biol Chem. 2008 Apr 11;283(15):9713-23. doi: 10.1074/jbc.M707275200. Epub 2008 , Jan 16. PMID:18201968 doi:http://dx.doi.org/10.1074/jbc.M707275200
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