|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of FOXA2 DNA binding domain bound to a full consensus DNA site== | | ==Crystal structure of FOXA2 DNA binding domain bound to a full consensus DNA site== |
| - | <StructureSection load='5x07' size='340' side='right' caption='[[5x07]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='5x07' size='340' side='right'caption='[[5x07]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5x07]] is a 12 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=5X07 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X07 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5x07]] is a 12 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=5X07 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X07 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FOXA2, HNF3B, TCF3B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.796Å</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=5x07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x07 OCA], [http://pdbe.org/5x07 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x07 RCSB], [http://www.ebi.ac.uk/pdbsum/5x07 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x07 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=5x07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x07 OCA], [https://pdbe.org/5x07 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x07 RCSB], [https://www.ebi.ac.uk/pdbsum/5x07 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x07 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FOXA2_HUMAN FOXA2_HUMAN]] Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). In embryonic development is required for notochord formation. Involved in the development of multiple endoderm-derived organ systems such as the liver, pancreas and lungs; FOXA1 and FOXA2 seem to have at least in part redundant roles. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; regulates the expression of genes important for glucose sensing in pancreatic beta-cells and glucose homeostasis. Involved in regulation of fat metabolism. Binds to fibrinogen beta promoter and is involved in IL6-induced fibrinogen beta transcriptional activation. | + | [https://www.uniprot.org/uniprot/FOXA2_HUMAN FOXA2_HUMAN] Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). In embryonic development is required for notochord formation. Involved in the development of multiple endoderm-derived organ systems such as the liver, pancreas and lungs; FOXA1 and FOXA2 seem to have at least in part redundant roles. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; regulates the expression of genes important for glucose sensing in pancreatic beta-cells and glucose homeostasis. Involved in regulation of fat metabolism. Binds to fibrinogen beta promoter and is involved in IL6-induced fibrinogen beta transcriptional activation. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 18: |
Line 18: |
| | </div> | | </div> |
| | <div class="pdbe-citations 5x07" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5x07" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[FOX 3D structures|FOX 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chen, L]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, X]] | + | [[Category: Chen L]] |
| - | [[Category: Chen, Y]] | + | [[Category: Chen X]] |
| - | [[Category: Chen, Z]] | + | [[Category: Chen Y]] |
| - | [[Category: Guo, M]] | + | [[Category: Chen Z]] |
| - | [[Category: Jiang, L]] | + | [[Category: Guo M]] |
| - | [[Category: Li, J]] | + | [[Category: Jiang L]] |
| - | [[Category: Qu, L]] | + | [[Category: Li J]] |
| - | [[Category: Wu, D]] | + | [[Category: Qu L]] |
| - | [[Category: Zhou, Z]] | + | [[Category: Wu D]] |
| - | [[Category: Consensus binding site]]
| + | [[Category: Zhou Z]] |
| - | [[Category: Dna binding protein-dna complex]]
| + | |
| - | [[Category: Forkhead domain]]
| + | |
| - | [[Category: Foxa2]]
| + | |
| - | [[Category: Isothermal titration calorimetry]]
| + | |
| - | [[Category: Itc]]
| + | |
| Structural highlights
Function
FOXA2_HUMAN Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). In embryonic development is required for notochord formation. Involved in the development of multiple endoderm-derived organ systems such as the liver, pancreas and lungs; FOXA1 and FOXA2 seem to have at least in part redundant roles. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; regulates the expression of genes important for glucose sensing in pancreatic beta-cells and glucose homeostasis. Involved in regulation of fat metabolism. Binds to fibrinogen beta promoter and is involved in IL6-induced fibrinogen beta transcriptional activation.
Publication Abstract from PubMed
FOXA2, a member of the forkhead family of transcription factors, plays essential roles in liver development and bile acid homeostasis. In this study, we report a 2.8 A co-crystal structure of the FOXA2 DNA-binding domain (FOXA2-DBD) bound to a DNA duplex containing a forkhead consensus binding site (GTAAACA). The FOXA2-DBD adopts the canonical winged-helix fold, with helix H3 and wing 1 regions mainly mediating the DNA recognition. Although the wing 2 region was not defined in the structure, isothermal titration calorimetry assays suggested that this region was required for optimal DNA binding. Structure comparison with the FOXA3-DBD bound to DNA revealed more major groove contacts and fewer minor groove contacts in the FOXA2 structure than in the FOXA3 structure. Structure comparison with the FOXO1-DBD bound to DNA showed that different forkhead proteins could induce different DNA conformations upon binding to identical DNA sequences. Our findings provide the structural basis for FOXA2 protein binding to a consensus forkhead site and elucidate how members of the forkhead protein family bind different DNA sites.
Structure of the Forkhead Domain of FOXA2 Bound to a Complete DNA Consensus Site.,Li J, Dantas Machado AC, Guo M, Sagendorf JM, Zhou Z, Jiang L, Chen X, Wu D, Qu L, Chen Z, Chen L, Rohs R, Chen Y Biochemistry. 2017 Jul 25;56(29):3745-3753. doi: 10.1021/acs.biochem.7b00211., Epub 2017 Jul 11. PMID:28644006[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Li J, Dantas Machado AC, Guo M, Sagendorf JM, Zhou Z, Jiang L, Chen X, Wu D, Qu L, Chen Z, Chen L, Rohs R, Chen Y. Structure of the Forkhead Domain of FOXA2 Bound to a Complete DNA Consensus Site. Biochemistry. 2017 Jul 25;56(29):3745-3753. doi: 10.1021/acs.biochem.7b00211., Epub 2017 Jul 11. PMID:28644006 doi:http://dx.doi.org/10.1021/acs.biochem.7b00211
|
