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| | ==C-terminal bZIP domain of human C/EBPbeta with 16bp Methylated Oligonucleotide Containing Consensus Recognition Sequence-C2221 Crystal Form== | | ==C-terminal bZIP domain of human C/EBPbeta with 16bp Methylated Oligonucleotide Containing Consensus Recognition Sequence-C2221 Crystal Form== |
| - | <StructureSection load='6mg2' size='340' side='right' caption='[[6mg2]], [[Resolution|resolution]] 1.93Å' scene=''> | + | <StructureSection load='6mg2' size='340' side='right'caption='[[6mg2]], [[Resolution|resolution]] 1.93Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6mg2]] is a 4 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=6MG2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MG2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6mg2]] is a 4 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=6MG2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MG2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.928Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CEBPB, TCF5, PP9092 ([http://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'>[https://proteopedia.org/fgij/fg.htm?mol=6mg2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mg2 OCA], [https://pdbe.org/6mg2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mg2 RCSB], [https://www.ebi.ac.uk/pdbsum/6mg2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mg2 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=6mg2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mg2 OCA], [http://pdbe.org/6mg2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mg2 RCSB], [http://www.ebi.ac.uk/pdbsum/6mg2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mg2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CEBPB_HUMAN CEBPB_HUMAN]] Important transcriptional activator in the regulation of genes involved in immune and inflammatory responses. Specifically binds to an IL-1 response element in the IL-6 gene. NF-IL6 also binds to regulatory regions of several acute-phase and cytokines genes. It probably plays a role in the regulation of acute-phase reaction, inflammation and hemopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Functions in brown adipose tissue (BAT) differentiation (By similarity). Regulates the transcriptional induction of peroxisome proliferator-activated receptor gamma (PPARG).<ref>PMID:20829347</ref> | + | [https://www.uniprot.org/uniprot/CEBPB_HUMAN CEBPB_HUMAN] Important transcriptional activator in the regulation of genes involved in immune and inflammatory responses. Specifically binds to an IL-1 response element in the IL-6 gene. NF-IL6 also binds to regulatory regions of several acute-phase and cytokines genes. It probably plays a role in the regulation of acute-phase reaction, inflammation and hemopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Functions in brown adipose tissue (BAT) differentiation (By similarity). Regulates the transcriptional induction of peroxisome proliferator-activated receptor gamma (PPARG).<ref>PMID:20829347</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Cheng, X]] | + | [[Category: Large Structures]] |
| - | [[Category: Horton, J R]] | + | [[Category: Cheng X]] |
| - | [[Category: Yang, J]] | + | [[Category: Horton JR]] |
| - | [[Category: Bzip transciption factor dna methylation cpa methylation protein-dna complex]] | + | [[Category: Yang J]] |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription-dna complex]]
| + | |
| Structural highlights
Function
CEBPB_HUMAN Important transcriptional activator in the regulation of genes involved in immune and inflammatory responses. Specifically binds to an IL-1 response element in the IL-6 gene. NF-IL6 also binds to regulatory regions of several acute-phase and cytokines genes. It probably plays a role in the regulation of acute-phase reaction, inflammation and hemopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Functions in brown adipose tissue (BAT) differentiation (By similarity). Regulates the transcriptional induction of peroxisome proliferator-activated receptor gamma (PPARG).[1]
Publication Abstract from PubMed
CCAAT/enhancer binding proteins (C/EBPs) regulate gene expression in a variety of cells/tissues/organs, during a range of developmental stages, under both physiological and pathological conditions. C/EBP-related transcription factors have a consensus binding specificity of 5'-TTG-CG-CAA-3', with a central CpG/CpG and two outer CpA/TpG dinucleotides. Methylation of the CpG and CpA sites generates a DNA element with every pyrimidine having a methyl group in the 5-carbon position (thymine or 5-methylcytosine (5mC)). To understand the effects of both CpG and CpA modification on a centrally-important transcription factor, we show that C/EBPbeta binds the methylated 8-bp element with modestly-increased (2.4-fold) binding affinity relative to the unmodified cognate sequence, while cytosine hydroxymethylation (particularly at the CpA sites) substantially decreased binding affinity (36-fold). The structure of C/EBPbeta DNA binding domain in complex with methylated DNA revealed that the methyl groups of the 5mCpA/TpG make van der Waals contacts with Val285 in C/EBPbeta. Arg289 recognizes the central 5mCpG by forming a methyl-Arg-G triad, and its conformation is constrained by Val285 and the 5mCpG methyl group. We substituted Val285 with Ala (V285A) in an Ala-Val dipeptide, to mimic the conserved Ala-Ala in many members of the basic leucine-zipper family of transcription factors, important in gene regulation, cell proliferation and oncogenesis. The V285A variant demonstrated a 90-fold binding preference for methylated DNA (particularly 5mCpA methylation) over the unmodified sequence. The smaller side chain of Ala285 permits Arg289 to adopt two alternative conformations, to interact in a similar fashion with either the central 5mCpG or the TpG of the opposite strand. Significantly, the best-studied cis-regulatory elements in RNA polymerase II promoters and enhancers have variable sequences corresponding to the central CpG or reduced to a single G:C base pair, but retain a conserved outer CpA sequence. Our analyses suggest an important modification-dependent CpA recognition by basic leucine-zipper transcription factors.
Structural basis for effects of CpA modifications on C/EBPbeta binding of DNA.,Yang J, Horton JR, Wang D, Ren R, Li J, Sun D, Huang Y, Zhang X, Blumenthal RM, Cheng X Nucleic Acids Res. 2018 Dec 19. pii: 5253051. doi: 10.1093/nar/gky1264. PMID:30566668[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Park SH, Choi HJ, Yang H, Do KH, Kim J, Lee DW, Moon Y. Endoplasmic reticulum stress-activated C/EBP homologous protein enhances nuclear factor-kappaB signals via repression of peroxisome proliferator-activated receptor gamma. J Biol Chem. 2010 Nov 12;285(46):35330-9. doi: 10.1074/jbc.M110.136259. Epub 2010, Sep 9. PMID:20829347 doi:10.1074/jbc.M110.136259
- ↑ Yang J, Horton JR, Wang D, Ren R, Li J, Sun D, Huang Y, Zhang X, Blumenthal RM, Cheng X. Structural basis for effects of CpA modifications on C/EBPbeta binding of DNA. Nucleic Acids Res. 2018 Dec 19. pii: 5253051. doi: 10.1093/nar/gky1264. PMID:30566668 doi:http://dx.doi.org/10.1093/nar/gky1264
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