|
|
| (4 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Crystal structure of monobody Mb(S4) bound to Prdm14 in complex with Mtgr1== | | ==Crystal structure of monobody Mb(S4) bound to Prdm14 in complex with Mtgr1== |
| - | <StructureSection load='5ecj' size='340' side='right' caption='[[5ecj]], [[Resolution|resolution]] 3.05Å' scene=''> | + | <StructureSection load='5ecj' size='340' side='right'caption='[[5ecj]], [[Resolution|resolution]] 3.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ecj]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ECJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ECJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ecj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ECJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ECJ FirstGlance]. <br> |
| - | </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=5ecj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ecj OCA], [http://pdbe.org/5ecj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ecj RCSB], [http://www.ebi.ac.uk/pdbsum/5ecj PDBsum]</span></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]] 3.05Å</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=5ecj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ecj OCA], [https://pdbe.org/5ecj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ecj RCSB], [https://www.ebi.ac.uk/pdbsum/5ecj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ecj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/MTG8R_MOUSE MTG8R_MOUSE] Required for tumorigenesis in a AOM/DSS colitis-associated carcinoma model. May be involved in intestinal tumorigenesis.<ref>PMID:21303973</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PRD14_MOUSE PRD14_MOUSE]] Transcription factor that has both positive and negative roles on transcription. Plays a role in cellular pluripotency (By similarity). Essential for germ cell development at 2 levels: the reacquisition of potential pluripotency, including SOX2 up-regulation, and successful epigenetic reprogramming, characterized by EHMT1 repression.<ref>PMID:18622394</ref> | + | [https://www.uniprot.org/uniprot/PRD14_MOUSE PRD14_MOUSE] Transcription factor that has both positive and negative roles on transcription. Plays a role in cellular pluripotency (By similarity). Essential for germ cell development at 2 levels: the reacquisition of potential pluripotency, including SOX2 up-regulation, and successful epigenetic reprogramming, characterized by EHMT1 repression.<ref>PMID:18622394</ref> [https://www.uniprot.org/uniprot/MTG8R_MOUSE MTG8R_MOUSE] Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes. Via association with PRDM14 is involved in regulation of embryonic stem cell (ESC) pluripotency. Involved in primordial germ cell (PCG) formation (PubMed:27281218). Stabilizes PRDM14 and OCT4 on chromatin in a homooligomerization-dependent mannerCan repress the expression of MMP7 in a ZBTB33-dependent manner (By similarity). Through heteromerization with CBFA2T3/MTG16 may be involved in regulation of the proliferation and the differentiation of erythroid progenitors by repressing the expression of TAL1 target genes (PubMed:19799863). Required for the maintenance of the secretory cell lineage in the small intestine (PubMed:16227606). Can inhibit Notch signaling probably by association with RBPJ and may be involved in GFI1-mediated Paneth cell differentiation (PubMed:25398765).[UniProtKB:O43439]<ref>PMID:16227606</ref> <ref>PMID:25398765</ref> <ref>PMID:27281218</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Prdm14 is a sequence-specific transcriptional regulator of embryonic stem cell (ESC) pluripotency and primordial germ cell (PGC) formation. It exerts its function, at least in part, through repressing genes associated with epigenetic modification and cell differentiation. Here, we show that this repressive function is mediated through an ETO-family co-repressor Mtgr1, which tightly binds to the pre-SET/SET domains of Prdm14 and co-occupies its genomic targets in mouse ESCs. We generated two monobodies, synthetic binding proteins, targeting the Prdm14 SET domain and demonstrate their utility, respectively, in facilitating crystallization and structure determination of the Prdm14-Mtgr1 complex, or as genetically encoded inhibitor of the Prdm14-Mtgr1 interaction. Structure-guided point mutants and the monobody abrogated the Prdm14-Mtgr1 association and disrupted Prdm14's function in mESC gene expression and PGC formation in vitro. Altogether, our work uncovers the molecular mechanism underlying Prdm14-mediated repression and provides renewable reagents for studying and controlling Prdm14 functions.
| + | |
| - | | + | |
| - | ETO family protein Mtgr1 mediates Prdm14 functions in stem cell maintenance and primordial germ cell formation.,Nady N, Gupta A, Ma Z, Swigut T, Koide A, Koide S, Wysocka J Elife. 2015 Nov 2;4. pii: e10150. doi: 10.7554/eLife.10150. PMID:26523391<ref>PMID:26523391</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| - | <div class="pdbe-citations 5ecj" style="background-color:#fffaf0;"></div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Gupta, A]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Koide, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Gene regulation-transcription complex]] | + | [[Category: Mus musculus]] |
| - | [[Category: Protein binding]] | + | [[Category: Gupta A]] |
| - | [[Category: Transferase]] | + | [[Category: Koide S]] |
| Structural highlights
Disease
MTG8R_MOUSE Required for tumorigenesis in a AOM/DSS colitis-associated carcinoma model. May be involved in intestinal tumorigenesis.[1]
Function
PRD14_MOUSE Transcription factor that has both positive and negative roles on transcription. Plays a role in cellular pluripotency (By similarity). Essential for germ cell development at 2 levels: the reacquisition of potential pluripotency, including SOX2 up-regulation, and successful epigenetic reprogramming, characterized by EHMT1 repression.[2] MTG8R_MOUSE Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes. Via association with PRDM14 is involved in regulation of embryonic stem cell (ESC) pluripotency. Involved in primordial germ cell (PCG) formation (PubMed:27281218). Stabilizes PRDM14 and OCT4 on chromatin in a homooligomerization-dependent mannerCan repress the expression of MMP7 in a ZBTB33-dependent manner (By similarity). Through heteromerization with CBFA2T3/MTG16 may be involved in regulation of the proliferation and the differentiation of erythroid progenitors by repressing the expression of TAL1 target genes (PubMed:19799863). Required for the maintenance of the secretory cell lineage in the small intestine (PubMed:16227606). Can inhibit Notch signaling probably by association with RBPJ and may be involved in GFI1-mediated Paneth cell differentiation (PubMed:25398765).[UniProtKB:O43439][3] [4] [5]
References
- ↑ Barrett CW, Fingleton B, Williams A, Ning W, Fischer MA, Washington MK, Chaturvedi R, Wilson KT, Hiebert SW, Williams CS. MTGR1 is required for tumorigenesis in the murine AOM/DSS colitis-associated carcinoma model. Cancer Res. 2011 Feb 15;71(4):1302-12. PMID:21303973 doi:10.1158/0008-5472.CAN-10-3317
- ↑ Yamaji M, Seki Y, Kurimoto K, Yabuta Y, Yuasa M, Shigeta M, Yamanaka K, Ohinata Y, Saitou M. Critical function of Prdm14 for the establishment of the germ cell lineage in mice. Nat Genet. 2008 Aug;40(8):1016-22. doi: 10.1038/ng.186. Epub 2008 Jul 11. PMID:18622394 doi:http://dx.doi.org/10.1038/ng.186
- ↑ Amann JM, Chyla BJ, Ellis TC, Martinez A, Moore AC, Franklin JL, McGhee L, Meyers S, Ohm JE, Luce KS, Ouelette AJ, Washington MK, Thompson MA, King D, Gautam S, Coffey RJ, Whitehead RH, Hiebert SW. Mtgr1 is a transcriptional corepressor that is required for maintenance of the secretory cell lineage in the small intestine. Mol Cell Biol. 2005 Nov;25(21):9576-85. PMID:16227606 doi:10.1128/MCB.25.21.9576-9585.2005
- ↑ Parang B, Rosenblatt D, Williams AD, Washington MK, Revetta F, Short SP, Reddy VK, Hunt A, Shroyer NF, Engel ME, Hiebert SW, Williams CS. The transcriptional corepressor MTGR1 regulates intestinal secretory lineage allocation. FASEB J. 2015 Mar;29(3):786-95. PMID:25398765 doi:10.1096/fj.14-254284
- ↑ Tu S, Narendra V, Yamaji M, Vidal SE, Rojas LA, Wang X, Kim SY, Garcia BA, Tuschl T, Stadtfeld M, Reinberg D. Co-repressor CBFA2T2 regulates pluripotency and germline development. Nature. 2016 Jun 16;534(7607):387-90. PMID:27281218 doi:10.1038/nature18004
|
