|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of the complex comprised of ETS1, RUNX1, CBFBETA, and the tcralpha gene enhancer DNA== | | ==Crystal structure of the complex comprised of ETS1, RUNX1, CBFBETA, and the tcralpha gene enhancer DNA== |
| - | <StructureSection load='3wts' size='340' side='right' caption='[[3wts]], [[Resolution|resolution]] 2.35Å' scene=''> | + | <StructureSection load='3wts' size='340' side='right'caption='[[3wts]], [[Resolution|resolution]] 2.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3wts]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [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=3WTS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WTS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3wts]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://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=3WTS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WTS FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3wtt|3wtt]], [[3wtu|3wtu]], [[3wtv|3wtv]], [[3wtw|3wtw]], [[3wtx|3wtx]], [[3wty|3wty]], [[3wtz|3wtz]], [[3wu0|3wu0]], [[3wu1|3wu1]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3wtt|3wtt]], [[3wtu|3wtu]], [[3wtv|3wtv]], [[3wtw|3wtw]], [[3wtx|3wtx]], [[3wty|3wty]], [[3wtz|3wtz]], [[3wu0|3wu0]], [[3wu1|3wu1]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Aml1, Cbfa2, Pebp2ab, Runx1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Cbfb, Pebp2b, Pebpb2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), ETS1, EWSR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Aml1, Cbfa2, Pebp2ab, Runx1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Cbfb, Pebp2b, Pebpb2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), ETS1, EWSR2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3wts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wts OCA], [http://pdbe.org/3wts PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wts RCSB], [http://www.ebi.ac.uk/pdbsum/3wts PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wts 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=3wts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wts OCA], [https://pdbe.org/3wts PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wts RCSB], [https://www.ebi.ac.uk/pdbsum/3wts PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wts ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/RUNX1_MOUSE RUNX1_MOUSE]] Note=Mice with an Runx1 lacking the DNA-binding region are found to die between embryonic days 11.5 to 12.5 due to hemorrhaging in the central nervous system. This hemorrhaging is preceded by necrosis and hematopoiesis is blocked. | + | [[https://www.uniprot.org/uniprot/RUNX1_MOUSE RUNX1_MOUSE]] Note=Mice with an Runx1 lacking the DNA-binding region are found to die between embryonic days 11.5 to 12.5 due to hemorrhaging in the central nervous system. This hemorrhaging is preceded by necrosis and hematopoiesis is blocked. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RUNX1_MOUSE RUNX1_MOUSE]] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL-3 and GM-CSF promoters. Essential for the development of normal hematopoiesis. Isoform 4 shows higher binding activities for target genes and binds TCR-beta-E2 and RAG-1 target site with threefold higher affinity than other isoforms. It is less effective in the context of neutrophil terminal differentiation. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the BLK promoter. Inhibits KAT6B-dependent transcriptional activation (By similarity).<ref>PMID:8565077</ref> <ref>PMID:8622955</ref> [[http://www.uniprot.org/uniprot/ETS1_HUMAN ETS1_HUMAN]] Transcription factor.<ref>PMID:10698492</ref> [[http://www.uniprot.org/uniprot/PEBB_MOUSE PEBB_MOUSE]] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters. CBFB enhances DNA binding by RUNX1. | + | [[https://www.uniprot.org/uniprot/RUNX1_MOUSE RUNX1_MOUSE]] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL-3 and GM-CSF promoters. Essential for the development of normal hematopoiesis. Isoform 4 shows higher binding activities for target genes and binds TCR-beta-E2 and RAG-1 target site with threefold higher affinity than other isoforms. It is less effective in the context of neutrophil terminal differentiation. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the BLK promoter. Inhibits KAT6B-dependent transcriptional activation (By similarity).<ref>PMID:8565077</ref> <ref>PMID:8622955</ref> [[https://www.uniprot.org/uniprot/ETS1_HUMAN ETS1_HUMAN]] Transcription factor.<ref>PMID:10698492</ref> [[https://www.uniprot.org/uniprot/PEBB_MOUSE PEBB_MOUSE]] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters. CBFB enhances DNA binding by RUNX1. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 21: |
Line 21: |
| | </div> | | </div> |
| | <div class="pdbe-citations 3wts" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3wts" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Core-binding factor|Core-binding factor]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 26: |
Line 29: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Hamada, K]] | | [[Category: Hamada, K]] |
| Structural highlights
3wts is a 10 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | |
| Gene: | Aml1, Cbfa2, Pebp2ab, Runx1 (LK3 transgenic mice), Cbfb, Pebp2b, Pebpb2 (LK3 transgenic mice), ETS1, EWSR2 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[RUNX1_MOUSE] Note=Mice with an Runx1 lacking the DNA-binding region are found to die between embryonic days 11.5 to 12.5 due to hemorrhaging in the central nervous system. This hemorrhaging is preceded by necrosis and hematopoiesis is blocked.
Function
[RUNX1_MOUSE] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL-3 and GM-CSF promoters. Essential for the development of normal hematopoiesis. Isoform 4 shows higher binding activities for target genes and binds TCR-beta-E2 and RAG-1 target site with threefold higher affinity than other isoforms. It is less effective in the context of neutrophil terminal differentiation. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the BLK promoter. Inhibits KAT6B-dependent transcriptional activation (By similarity).[1] [2] [ETS1_HUMAN] Transcription factor.[3] [PEBB_MOUSE] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters. CBFB enhances DNA binding by RUNX1.
Publication Abstract from PubMed
Cooperative assemblies of transcription factors (TFs) on target gene enhancers coordinate cell proliferation, fate specification, and differentiation through precise and complicated transcriptional mechanisms. Chemical modifications, such as phosphorylation, of TFs induced by cell signaling, further modulate the dynamic cooperativity of TFs. In this study, we found that various Ets1-containing TF-DNA complexes respond differently to calcium-induced phosphorylation of Ets1, which is known to inhibit Ets1-DNA binding. Crystallographic analysis of a complex comprising Ets1, Runx1, and CBFbeta at the TCRalpha enhancer, revealed that Ets1 acquires robust binding stability in the Runx1 and DNA-complexed state, via allosteric mechanisms. This allows phosphorylated Ets1 to be retained at the TCRalpha enhancer with Runx1, in contrast to other Ets1 target gene enhancers including mb-1 and stromelysin-1. This study provides a structure-based model for cell signaling-dependent regulation of target genes, mediated via chemical modification of TFs.
A novel allosteric mechanism on protein-DNA interactions underlying the phosphorylation-dependent regulation of Ets1 target gene expressions.,Shiina M, Hamada K, Inoue-Bungo T, Shimamura M, Uchiyama A, Baba S, Sato K, Yamamoto M, Ogata K J Mol Biol. 2014 Jul 29. pii: S0022-2836(14)00368-4. doi:, 10.1016/j.jmb.2014.07.020. PMID:25083921[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell. 1996 Jan 26;84(2):321-30. PMID:8565077
- ↑ Wang Q, Stacy T, Binder M, Marin-Padilla M, Sharpe AH, Speck NA. Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3444-9. PMID:8622955
- ↑ Li R, Pei H, Watson DK, Papas TS. EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes. Oncogene. 2000 Feb 10;19(6):745-53. PMID:10698492 doi:10.1038/sj.onc.1203385
- ↑ Shiina M, Hamada K, Inoue-Bungo T, Shimamura M, Uchiyama A, Baba S, Sato K, Yamamoto M, Ogata K. A novel allosteric mechanism on protein-DNA interactions underlying the phosphorylation-dependent regulation of Ets1 target gene expressions. J Mol Biol. 2014 Jul 29. pii: S0022-2836(14)00368-4. doi:, 10.1016/j.jmb.2014.07.020. PMID:25083921 doi:http://dx.doi.org/10.1016/j.jmb.2014.07.020
|
