7upz
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structural basis for cell type specific DNA binding of C/EBPbeta: the case of cell cycle inhibitor p15INK4b promoter== | |
| + | <StructureSection load='7upz' size='340' side='right'caption='[[7upz]], [[Resolution|resolution]] 2.49Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7upz]] 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=7UPZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UPZ FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.487Å</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=7upz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7upz OCA], [https://pdbe.org/7upz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7upz RCSB], [https://www.ebi.ac.uk/pdbsum/7upz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7upz ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | C/EBPbeta is a key regulator of numerous cellular processes, but it can also contribute to tumorigenesis and viral diseases. It binds to specific DNA sequences (C/EBP sites) and interacts with other transcription factors to control expression of multiple eukaryotic genes in a tissue and cell-type dependent manner. A body of evidence has established that cell-type-specific regulatory information is contained in the local DNA sequence of the binding motif. In human epithelial cells, C/EBPbeta is an essential cofactor for TGFbeta signaling in the case of Smad2/3/4 and FoxO-dependent induction of the cell cycle inhibitor, p15INK4b. In the TGFbeta-responsive region 2 of the p15INK4b promoter, the Smad binding site is flanked by a C/EBP site, CTTAA*GAAAG, which differs from the canonical, palindromic ATTGC*GCAAT motif. The X-ray crystal structure of C/EBPbeta bound to the p15INK4b promoter fragment shows how GCGC-to-AAGA substitution generates changes in the intermolecular interactions in the protein-DNA interface that enhances C/EBPbeta binding specificity, limits possible epigenetic regulation of the promoter, and generates a DNA element with a unique pattern of methyl groups in the major groove. Significantly, CT/GA dinucleotides located at the 5'ends of the double stranded element maintain local narrowing of the DNA minor groove width that is necessary for DNA recognition. Our results suggest that C/EBPbeta would accept all forms of modified cytosine in the context of the CpT site. This contrasts with the effect on the consensus motif, where C/EBPbeta binding is modestly increased by cytosine methylation, but substantially decreased by hydroxymethylation. | ||
| - | + | Structural basis for cell type specific DNA binding of C/EBPbeta: The case of cell cycle inhibitor p15INK4b promoter.,Lountos GT, Cherry S, Tropea JE, Wlodawer A, Miller M J Struct Biol. 2022 Nov 4;214(4):107918. doi: 10.1016/j.jsb.2022.107918. PMID:36343842<ref>PMID:36343842</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7upz" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Cherry S]] | ||
| + | [[Category: Lountos GT]] | ||
| + | [[Category: Miller M]] | ||
| + | [[Category: Tropea JE]] | ||
| + | [[Category: Wlodawer A]] | ||
Current revision
Structural basis for cell type specific DNA binding of C/EBPbeta: the case of cell cycle inhibitor p15INK4b promoter
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