4x9j

From Proteopedia

(Difference between revisions)

Current revision

EGR-1 with Doubly Methylated DNA

Structural highlights

4x9j is a 3 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.412Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EGR1_HUMAN Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-CGCCCCCGC-3'(EGR-site). Activates the transcription of target genes whose products are required for mitogenesis and differentiation.

Publication Abstract from PubMed

The inducible transcription factor Egr-1 binds specifically to 9-bp target sequences containing two CpG sites that can potentially be methylated at four cytosine bases. Although it appears that complete CpG methylation would make an unfavorable steric clash in the previous crystal structures of the complexes with unmethylated or partially methylated DNA, our affinity data suggest that DNA recognition by Egr-1 is insensitive to CpG methylation. We have determined, at a 1.4-A resolution, the crystal structure of the Egr-1 zinc-finger complex with completely methylated target DNA. Structural comparison of the three different methylation states reveals why Egr-1 can recognize the target sequences regardless of CpG methylation.

Structural impact of complete CpG methylation within target DNA on specific complex formation of the inducible transcription factor Egr-1.,Zandarashvili L, White MA, Esadze A, Iwahara J FEBS Lett. 2015 May 19. pii: S0014-5793(15)00398-1. doi:, 10.1016/j.febslet.2015.05.022. PMID:25999311^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zandarashvili L, White MA, Esadze A, Iwahara J. Structural impact of complete CpG methylation within target DNA on specific complex formation of the inducible transcription factor Egr-1. FEBS Lett. 2015 May 19. pii: S0014-5793(15)00398-1. doi:, 10.1016/j.febslet.2015.05.022. PMID:25999311 doi:http://dx.doi.org/10.1016/j.febslet.2015.05.022

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/4x9j"

@@ Line 1: / Line 1: @@
 ==EGR-1 with Doubly Methylated DNA==
-<StructureSection load='4x9j' size='340' side='right' caption='[[4x9j]], [[Resolution|resolution]] 1.41&Aring;' scene=''>
+<StructureSection load='4x9j' size='340' side='right'caption='[[4x9j]], [[Resolution|resolution]] 1.41&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4x9j]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X9J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X9J FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4x9j]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X9J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X9J FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 1.412&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene></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=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4r2a|4r2a]]</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=4x9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x9j OCA], [https://pdbe.org/4x9j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x9j RCSB], [https://www.ebi.ac.uk/pdbsum/4x9j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x9j ProSAT]</span></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=4x9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x9j OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4x9j RCSB], [http://www.ebi.ac.uk/pdbsum/4x9j PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/EGR1_HUMAN EGR1_HUMAN]] Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-CGCCCCCGC-3'(EGR-site). Activates the transcription of target genes whose products are required for mitogenesis and differentiation.
+[https://www.uniprot.org/uniprot/EGR1_HUMAN EGR1_HUMAN] Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-CGCCCCCGC-3'(EGR-site). Activates the transcription of target genes whose products are required for mitogenesis and differentiation.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
-In mammalian DNA, cytosine occurs in several chemical forms, including unmodified cytosine (C), 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5mC is a major epigenetic signal that acts to regulate gene expression. 5hmC, 5fC, and 5caC are oxidized derivatives that might also act as distinct epigenetic signals. We investigated the response of the zinc finger DNA-binding domains of transcription factors early growth response protein 1 (Egr1) and Wilms tumor protein 1 (WT1) to different forms of modified cytosine within their recognition sequence, 5'-GCG(T/G)GGGCG-3'. Both displayed high affinity for the sequence when C or 5mC was present and much reduced affinity when 5hmC or 5fC was present, indicating that they differentiate primarily oxidized C from unoxidized C, rather than methylated C from unmethylated C. 5caC affected the two proteins differently, abolishing binding by Egr1 but not by WT1. We ascribe this difference to electrostatic interactions in the binding sites. In Egr1, a negatively charged glutamate conflicts with the negatively charged carboxylate of 5caC, whereas the corresponding glutamine of WT1 interacts with this group favorably. Our analyses shows that zinc finger proteins (and their splice variants) can respond in modulated ways to alternative modifications within their binding sequence.
+The inducible transcription factor Egr-1 binds specifically to 9-bp target sequences containing two CpG sites that can potentially be methylated at four cytosine bases. Although it appears that complete CpG methylation would make an unfavorable steric clash in the previous crystal structures of the complexes with unmethylated or partially methylated DNA, our affinity data suggest that DNA recognition by Egr-1 is insensitive to CpG methylation. We have determined, at a 1.4-A resolution, the crystal structure of the Egr-1 zinc-finger complex with completely methylated target DNA. Structural comparison of the three different methylation states reveals why Egr-1 can recognize the target sequences regardless of CpG methylation.
-Wilms tumor protein recognizes 5-carboxylcytosine within a specific DNA sequence.,Hashimoto H, Olanrewaju YO, Zheng Y, Wilson GG, Zhang X, Cheng X Genes Dev. 2014 Sep 25. pii: gad.250746.114. PMID:25258363<ref>PMID:25258363</ref>
+Structural impact of complete CpG methylation within target DNA on specific complex formation of the inducible transcription factor Egr-1.,Zandarashvili L, White MA, Esadze A, Iwahara J FEBS Lett. 2015 May 19. pii: S0014-5793(15)00398-1. doi:, 10.1016/j.febslet.2015.05.022. PMID:25999311<ref>PMID:25999311</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4x9j" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Iwahara, J]]
+[[Category: Homo sapiens]]
-[[Category: White, M A]]
+[[Category: Large Structures]]
-[[Category: Zandarashvili, L]]
+[[Category: Synthetic construct]]
-[[Category: Dna binding]]
+[[Category: Iwahara J]]
-[[Category: Methylated dna]]
+[[Category: White MA]]
-[[Category: Transcription]]
+[[Category: Zandarashvili L]]
-[[Category: Transcription regulator-dna complex]]
-[[Category: Zinc finger]]

4x9j

From Proteopedia

Current revision

EGR-1 with Doubly Methylated DNA

Structural highlights

Function

Publication Abstract from PubMed

References

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