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| | <StructureSection load='6o5k' size='340' side='right'caption='[[6o5k]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='6o5k' size='340' side='right'caption='[[6o5k]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6o5k]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O5K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O5K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6o5k]] 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=6O5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O5K 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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></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='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=6o5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5k OCA], [http://pdbe.org/6o5k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o5k RCSB], [http://www.ebi.ac.uk/pdbsum/6o5k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5k 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=6o5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5k OCA], [https://pdbe.org/6o5k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o5k RCSB], [https://www.ebi.ac.uk/pdbsum/6o5k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5k ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TIF1B_MOUSE TIF1B_MOUSE]] Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (PubMed:20164836). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (By similarity). Acts as a corepressor for ZFP568 (PubMed:22110054, PubMed:27658112).[UniProtKB:Q13263]<ref>PMID:20164836</ref> <ref>PMID:21518874</ref> <ref>PMID:22110054</ref> <ref>PMID:27658112</ref> <ref>PMID:9742105</ref> | + | [https://www.uniprot.org/uniprot/TIF1B_MOUSE TIF1B_MOUSE] Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (PubMed:20164836). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (By similarity). Acts as a corepressor for ZFP568 (PubMed:22110054, PubMed:27658112).[UniProtKB:Q13263]<ref>PMID:20164836</ref> <ref>PMID:21518874</ref> <ref>PMID:22110054</ref> <ref>PMID:27658112</ref> <ref>PMID:9742105</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | TRIM28 (also known as KAP1 or TIF1beta) is the universal co-repressor of the Kruppel-associated box-containing zinc finger proteins (Krab-ZFPs), the largest family of transcription factors in mammals. During early embryogenesis, TRIM28 mediates the transcriptional silencing of many endogenous retroviral elements and genomic imprinted sites. Silencing is initiated by the recruitment of TRIM28 to a target locus by members of the Krab-ZFP. Subsequently, TRIM28 functions as a scaffold protein to recruit chromatin modifying effectors featuring SETDB1, HP1 and the NuRD complex. Although many protein partners involved in silencing have been identified, the molecular basis of the protein interactions that mediate silencing remains largely unclear. In the present study, we identified the first Bbox domain (T28_B1 135-203) as a molecular interface responsible for the formation of higher-order oligomers of TRIM28. The structure of this domain reveals a new interface on the surface of the Bbox domain. Mutants disrupting the interface disrupt the formation of oligomers but have no observed effect on transcriptional silencing defining a single TRIM28 dimer as the functional unit for silencing. Using assembly-deficient mutants, we employed small-angle X-ray scattering and biophysical techniques to characterize binding to member of the Krab-ZFP family. This allows us to narrow and define the binding interface to the center of the coiled-coil region (residues 294-321) of TRIM28 and define mutants that abolish binding to the Krab-ZFP proteins.
| + | |
| | | | |
| - | A Dissection of Oligomerization by the TRIM28 Tripartite Motif and the Interaction with Members of the Krab-ZFP Family.,Sun Y, Keown JR, Black MM, Raclot C, Demarais N, Trono D, Turelli P, Goldstone DC J Mol Biol. 2019 May 9. pii: S0022-2836(19)30256-6. doi:, 10.1016/j.jmb.2019.05.002. PMID:31078555<ref>PMID:31078555</ref>
| + | ==See Also== |
| - | | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6o5k" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: RING-type E3 ubiquitin transferase]] | + | [[Category: Mus musculus]] |
| - | [[Category: Goldstone, D C]] | + | [[Category: Goldstone DC]] |
| - | [[Category: Keown, J R]] | + | [[Category: Keown JR]] |
| - | [[Category: Sun, Y]] | + | [[Category: Sun Y]] |
| - | [[Category: B-box kap1 tif1beta krab-zfp co-repressor]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
TIF1B_MOUSE Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (PubMed:20164836). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (By similarity). Acts as a corepressor for ZFP568 (PubMed:22110054, PubMed:27658112).[UniProtKB:Q13263][1] [2] [3] [4] [5]
See Also
References
- ↑ Matsui T, Leung D, Miyashita H, Maksakova IA, Miyachi H, Kimura H, Tachibana M, Lorincz MC, Shinkai Y. Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature. 2010 Apr 8;464(7290):927-31. doi: 10.1038/nature08858. Epub 2010 Feb 17. PMID:20164836 doi:http://dx.doi.org/10.1038/nature08858
- ↑ Okazaki IM, Okawa K, Kobayashi M, Yoshikawa K, Kawamoto S, Nagaoka H, Shinkura R, Kitawaki Y, Taniguchi H, Natsume T, Iemura S, Honjo T. Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation. Proc Natl Acad Sci U S A. 2011 May 10;108(19):7920-5. doi:, 10.1073/pnas.1104423108. Epub 2011 Apr 25. PMID:21518874 doi:http://dx.doi.org/10.1073/pnas.1104423108
- ↑ Shibata M, Blauvelt KE, Liem KF Jr, Garcia-Garcia MJ. TRIM28 is required by the mouse KRAB domain protein ZFP568 to control convergent extension and morphogenesis of extra-embryonic tissues. Development. 2011 Dec;138(24):5333-43. doi: 10.1242/dev.072546. PMID:22110054 doi:http://dx.doi.org/10.1242/dev.072546
- ↑ Murphy KE, Shylo NA, Alexander KA, Churchill AJ, Copperman C, Garcia-Garcia MJ. The Transcriptional Repressive Activity of KRAB Zinc Finger Proteins Does Not Correlate with Their Ability to Recruit TRIM28. PLoS One. 2016 Sep 22;11(9):e0163555. doi: 10.1371/journal.pone.0163555., eCollection 2016. PMID:27658112 doi:http://dx.doi.org/10.1371/journal.pone.0163555
- ↑ Chang CJ, Chen YL, Lee SC. Coactivator TIF1beta interacts with transcription factor C/EBPbeta and glucocorticoid receptor to induce alpha1-acid glycoprotein gene expression. Mol Cell Biol. 1998 Oct;18(10):5880-7. PMID:9742105
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