6lbm
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Crystal Structure of FOXC2-DBD bound to a palindromic DNA sequence== |
| - | <StructureSection load='6lbm' size='340' side='right'caption='[[6lbm]]' scene=''> | + | <StructureSection load='6lbm' size='340' side='right'caption='[[6lbm]], [[Resolution|resolution]] 2.84Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6lbm]] is a 3 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=6LBM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LBM FirstGlance]. <br> |
| - | </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=6lbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lbm OCA], [https://pdbe.org/6lbm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lbm RCSB], [https://www.ebi.ac.uk/pdbsum/6lbm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lbm ProSAT]</span></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]] 2.841Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=6lbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lbm OCA], [https://pdbe.org/6lbm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lbm RCSB], [https://www.ebi.ac.uk/pdbsum/6lbm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lbm ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/FOXC2_HUMAN FOXC2_HUMAN] Defects in FOXC2 are the cause of lymphedema hereditary type 2 (LMPH2) [MIM:[https://omim.org/entry/153200 153200]; also known as Meige lymphedema. Hereditary lymphedema is a chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections, and physical impairment.<ref>PMID:11078474</ref> Defects in FOXC2 are a cause of lymphedema-yellow nails (LYYN) [MIM:[https://omim.org/entry/153300 153300]. LYYN is characterized by yellow, dystrophic, thick and slowly growing nails, associated with lymphedema and respiratory involvement. Lymphedema occurs more often in the lower limbs. It can appear at birth or later in life. Onset generally follows the onset of ungual abnormalities. Defects in FOXC2 are a cause of lymphedema-distichiasis (LYD) [MIM:[https://omim.org/entry/153400 153400]. LYD is characterized by primary limb lymphedema usually starting at puberty (but in some cases later or at birth) and associated with distichiasis (double rows of eyelashes, with extra eyelashes growing from the Meibomian gland orifices).<ref>PMID:11499682</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/FOXC2_HUMAN FOXC2_HUMAN] Transcriptional activator. Might be involved in the formation of special mesenchymal tissues.<ref>PMID:9169153</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Forkhead transcription factors bind a canonical consensus DNA motif, RYAAAYA (R = A/G, Y = C/T), as a monomer. However, the molecular mechanisms by which forkhead transcription factors bind DNA as a dimer are not well understood. In this study, we show that FOXO1 recognizes a palindromic DNA element DIV2, and mediates transcriptional regulation. The crystal structure of FOXO1/DIV2 reveals that the FOXO1 DNA binding domain (DBD) binds the DIV2 site as a homodimer. The wing1 region of FOXO1 mediates the dimerization, which enhances FOXO1 DNA binding affinity and complex stability. Further biochemical assays show that FOXO3, FOXM1 and FOXI1 also bind the DIV2 site as homodimer, while FOXC2 can only bind this site as a monomer. Our structural, biochemical and bioinformatics analyses not only provide a novel mechanism by which FOXO1 binds DNA as a homodimer, but also shed light on the target selection of forkhead transcription factors. | ||
| + | |||
| + | Mechanism of forkhead transcription factors binding to a novel palindromic DNA site.,Li J, Dai S, Chen X, Liang X, Qu L, Jiang L, Guo M, Zhou Z, Wei H, Zhang H, Chen Z, Chen L, Chen Y Nucleic Acids Res. 2021 Apr 6;49(6):3573-3583. doi: 10.1093/nar/gkab086. PMID:33577686<ref>PMID:33577686</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6lbm" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[FOX 3D structures|FOX 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Dai SY]] |
| + | [[Category: Li J]] | ||
Current revision
Crystal Structure of FOXC2-DBD bound to a palindromic DNA sequence
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