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- | [[Image:2wbu.png|left|200px]] | |
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- | <!-- | + | ==CRYSTAL STRUCTURE OF THE ZINC FINGER DOMAIN OF KLF4 BOUND TO ITS TARGET DNA== |
- | The line below this paragraph, containing "STRUCTURE_2wbu", creates the "Structure Box" on the page.
| + | <StructureSection load='2wbu' size='340' side='right'caption='[[2wbu]], [[Resolution|resolution]] 2.50Å' scene=''> |
- | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
- | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[2wbu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WBU FirstGlance]. <br> |
- | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
- | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
- | {{STRUCTURE_2wbu| PDB=2wbu | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wbu OCA], [https://pdbe.org/2wbu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wbu RCSB], [https://www.ebi.ac.uk/pdbsum/2wbu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wbu ProSAT]</span></td></tr> |
| + | </table> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/KLF4_MOUSE KLF4_MOUSE] Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription (By similarity).<ref>PMID:10556311</ref> <ref>PMID:10431239</ref> <ref>PMID:15358627</ref> <ref>PMID:16954384</ref> <ref>PMID:17060454</ref> <ref>PMID:19816951</ref> <ref>PMID:20071344</ref> |
| + | == Evolutionary Conservation == |
| + | [[Image:Consurf_key_small.gif|200px|right]] |
| + | Check<jmol> |
| + | <jmolCheckbox> |
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wb/2wbu_consurf.spt"</scriptWhenChecked> |
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| + | </jmolCheckbox> |
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wbu ConSurf]. |
| + | <div style="clear:both"></div> |
| + | <div style="background-color:#fffaf0;"> |
| + | == Publication Abstract from PubMed == |
| + | Krueppel-like factor 4 (Klf4) belongs to the Sp/Klf family of zinc-finger transcription factors and is indispensable for terminal maturation of epithelial tissues. Furthermore, it is part of a small set of proteins that are used to generate pluripotent embryonic stem cells from differentiated tissues. Herein, we describe that a Klf4 zinc-finger domain mutant induces self-renewal and block of maturation, while wild-type Klf4 induces terminal macrophage differentiation. Moreover, we present the crystal structure of the zinc-finger domain of Klf4 bound to its target DNA, revealing that primarily the two C-terminal zinc-finger motifs are required for site specificity. Lack of those two zinc fingers leads to deficiency of Klf4 to induce macrophage differentiation. The first zinc finger, on the other hand, inhibits the otherwise cryptic self-renewal and block of differentiation activity of Klf4. Our data show that impairing the DNA binding could potentially contribute to a monocytic leukemia. |
| | | |
- | ===CRYSTAL STRUCTURE OF THE ZINC FINGER DOMAIN OF KLF4 BOUND TO ITS TARGET DNA===
| + | The structure of the Klf4 DNA-binding domain links to self-renewal and macrophage differentiation.,Schuetz A, Nana D, Rose C, Zocher G, Milanovic M, Koenigsmann J, Blasig R, Heinemann U, Carstanjen D Cell Mol Life Sci. 2011 Sep;68(18):3121-31. Epub 2011 Feb 3. PMID:21290164<ref>PMID:21290164</ref> |
| | | |
- | | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
- | <!--
| + | </div> |
- | The line below this paragraph, {{ABSTRACT_PUBMED_21290164}}, adds the Publication Abstract to the page
| + | <div class="pdbe-citations 2wbu" style="background-color:#fffaf0;"></div> |
- | (as it appears on PubMed at http://www.pubmed.gov), where 21290164 is the PubMed ID number.
| + | == References == |
- | -->
| + | <references/> |
- | {{ABSTRACT_PUBMED_21290164}}
| + | __TOC__ |
- | | + | </StructureSection> |
- | ==About this Structure== | + | [[Category: Large Structures]] |
- | [[2wbu]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WBU OCA].
| + | |
- | | + | |
- | ==Reference== | + | |
- | <ref group="xtra">PMID:021290164</ref><references group="xtra"/> | + | |
| [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
- | [[Category: Carstanjen, D.]] | + | [[Category: Carstanjen D]] |
- | [[Category: Heinemann, U.]] | + | [[Category: Heinemann U]] |
- | [[Category: Schuetz, A.]] | + | [[Category: Schuetz A]] |
- | [[Category: Zocher, G.]] | + | [[Category: Zocher G]] |
- | [[Category: Activator]]
| + | |
- | [[Category: Dna-binding]]
| + | |
- | [[Category: Metal-binding]]
| + | |
- | [[Category: Nucleus]]
| + | |
- | [[Category: Transcription]]
| + | |
- | [[Category: Transcription regulation]]
| + | |
- | [[Category: Transcription-dna complex]]
| + | |
- | [[Category: Zinc-finger]]
| + | |
| Structural highlights
Function
KLF4_MOUSE Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription (By similarity).[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Krueppel-like factor 4 (Klf4) belongs to the Sp/Klf family of zinc-finger transcription factors and is indispensable for terminal maturation of epithelial tissues. Furthermore, it is part of a small set of proteins that are used to generate pluripotent embryonic stem cells from differentiated tissues. Herein, we describe that a Klf4 zinc-finger domain mutant induces self-renewal and block of maturation, while wild-type Klf4 induces terminal macrophage differentiation. Moreover, we present the crystal structure of the zinc-finger domain of Klf4 bound to its target DNA, revealing that primarily the two C-terminal zinc-finger motifs are required for site specificity. Lack of those two zinc fingers leads to deficiency of Klf4 to induce macrophage differentiation. The first zinc finger, on the other hand, inhibits the otherwise cryptic self-renewal and block of differentiation activity of Klf4. Our data show that impairing the DNA binding could potentially contribute to a monocytic leukemia.
The structure of the Klf4 DNA-binding domain links to self-renewal and macrophage differentiation.,Schuetz A, Nana D, Rose C, Zocher G, Milanovic M, Koenigsmann J, Blasig R, Heinemann U, Carstanjen D Cell Mol Life Sci. 2011 Sep;68(18):3121-31. Epub 2011 Feb 3. PMID:21290164[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mahatan CS, Kaestner KH, Geiman DE, Yang VW. Characterization of the structure and regulation of the murine gene encoding gut-enriched Kruppel-like factor (Kruppel-like factor 4). Nucleic Acids Res. 1999 Dec 1;27(23):4562-9. PMID:10556311
- ↑ Segre JA, Bauer C, Fuchs E. Klf4 is a transcription factor required for establishing the barrier function of the skin. Nat Genet. 1999 Aug;22(4):356-60. PMID:10431239 doi:http://dx.doi.org/10.1038/11926
- ↑ Li Y, McClintick J, Zhong L, Edenberg HJ, Yoder MC, Chan RJ. Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4. Blood. 2005 Jan 15;105(2):635-7. Epub 2004 Sep 9. PMID:15358627 doi:http://dx.doi.org/10.1182/blood-2004-07-2681
- ↑ Nakatake Y, Fukui N, Iwamatsu Y, Masui S, Takahashi K, Yagi R, Yagi K, Miyazaki J, Matoba R, Ko MS, Niwa H. Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Mol Cell Biol. 2006 Oct;26(20):7772-82. Epub 2006 Sep 5. PMID:16954384 doi:http://dx.doi.org/10.1128/MCB.00468-06
- ↑ Swamynathan SK, Katz JP, Kaestner KH, Ashery-Padan R, Crawford MA, Piatigorsky J. Conditional deletion of the mouse Klf4 gene results in corneal epithelial fragility, stromal edema, and loss of conjunctival goblet cells. Mol Cell Biol. 2007 Jan;27(1):182-94. Epub 2006 Oct 23. PMID:17060454 doi:http://dx.doi.org/10.1128/MCB.00846-06
- ↑ Wei Z, Yang Y, Zhang P, Andrianakos R, Hasegawa K, Lyu J, Chen X, Bai G, Liu C, Pera M, Lu W. Klf4 interacts directly with Oct4 and Sox2 to promote reprogramming. Stem Cells. 2009 Dec;27(12):2969-78. doi: 10.1002/stem.231. PMID:19816951 doi:http://dx.doi.org/10.1002/stem.231
- ↑ Zhang P, Andrianakos R, Yang Y, Liu C, Lu W. Kruppel-like factor 4 (Klf4) prevents embryonic stem (ES) cell differentiation by regulating Nanog gene expression. J Biol Chem. 2010 Mar 19;285(12):9180-9. doi: 10.1074/jbc.M109.077958. Epub 2010 , Jan 13. PMID:20071344 doi:http://dx.doi.org/10.1074/jbc.M109.077958
- ↑ Schuetz A, Nana D, Rose C, Zocher G, Milanovic M, Koenigsmann J, Blasig R, Heinemann U, Carstanjen D. The structure of the Klf4 DNA-binding domain links to self-renewal and macrophage differentiation. Cell Mol Life Sci. 2011 Sep;68(18):3121-31. Epub 2011 Feb 3. PMID:21290164 doi:10.1007/s00018-010-0618-x
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