4m9e: Difference between revisions

Latest revision as of 16:34, 20 September 2023

Structure of Klf4 zinc finger DNA binding domain in complex with methylated DNA

Structural highlights

4m9e is a 3 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.851Å
Ligands:	5CM, ACT, GOL, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

Transcription factor Kruppel-like factor 4 (Klf4), one of the factors directing cellular reprogramming, recognizes the CpG dinucleotide (whether methylated or unmodified) within a specific G/C-rich sequence. The binding affinity of the mouse Klf4 DNA-binding domain for methylated DNA is only slightly stronger than that for an unmodified oligonucleotide. The structure of the C-terminal three Kruppel-like zinc fingers (ZnFs) of mouse Klf4, in complex with fully methylated DNA, was determined at 1.85 A resolution. An arginine and a glutamate interact with the methyl group. By comparison with two other recently characterized structures of ZnF protein complexes with methylated DNA, we propose a common principle of recognition of methylated CpG by C2H2 ZnF proteins, which involves a spatially conserved Arg-Glu pair.

Structural basis for Klf4 recognition of methylated DNA.,Liu Y, Olanrewaju YO, Zheng Y, Hashimoto H, Blumenthal RM, Zhang X, Cheng X Nucleic Acids Res. 2014 Feb 11. PMID:24520114^[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:https://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:https://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:https://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:https://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:https://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:https://dx.doi.org/10.1074/jbc.M109.077958
↑ Liu Y, Olanrewaju YO, Zheng Y, Hashimoto H, Blumenthal RM, Zhang X, Cheng X. Structural basis for Klf4 recognition of methylated DNA. Nucleic Acids Res. 2014 Feb 11. PMID:24520114 doi:https://dx.doi.org/10.1093/nar/gku134

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OCA

[1] 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

[2] 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:https://dx.doi.org/10.1038/11926

[3] 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:https://dx.doi.org/10.1182/blood-2004-07-2681

[4] 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:https://dx.doi.org/10.1128/MCB.00468-06

[5] 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:https://dx.doi.org/10.1128/MCB.00846-06

[6] 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:https://dx.doi.org/10.1002/stem.231

[7] 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:https://dx.doi.org/10.1074/jbc.M109.077958

[8] Liu Y, Olanrewaju YO, Zheng Y, Hashimoto H, Blumenthal RM, Zhang X, Cheng X. Structural basis for Klf4 recognition of methylated DNA. Nucleic Acids Res. 2014 Feb 11. PMID:24520114 doi:https://dx.doi.org/10.1093/nar/gku134

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@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4m9e]] 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=4M9E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M9E FirstGlance]. <br>
-</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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.851&#8491;</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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4m9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m9e OCA], [https://pdbe.org/4m9e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m9e RCSB], [https://www.ebi.ac.uk/pdbsum/4m9e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m9e ProSAT]</span></td></tr>
 </table>

4m9e: Difference between revisions

Latest revision as of 16:34, 20 September 2023

Structure of Klf4 zinc finger DNA binding domain in complex with methylated DNA

Structural highlights

Function

Publication Abstract from PubMed

References

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