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4m9v

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Revision as of 19:06, 4 August 2016

Zfp57 mutant (E182Q) in complex with 5-carboxylcytosine DNA

Structural highlights

4m9v is a 6 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
NonStd Res:	,
Related:	4gzn
Gene:	Zfp57 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ZFP57_MOUSE] Transcription regulator required to maintain maternal and paternal gene imprinting, a process by which gene expression is restricted in a parent of origin-specific manner by epigenetic modification of genomic DNA and chromatin, including DNA methylation. Acts by controlling DNA methylation during the earliest multicellular stages of development at multiple imprinting control regions. Required for the establishment of maternal methylation imprints at SNRPN locus. Acts as a transcriptional repressor in Schwann cells. Binds to a 5'-TGCCGC-3' consensus sequence and recognizes the methylated CpG within this element.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The Zfp57 gene encodes a KRAB (Kruppel-associated box) domain-containing C2H2 zinc finger transcription factor that is expressed in early development. Zfp57 protein recognizes methylated CpG dinucleotide within GCGGCA elements at multiple imprinting control regions. In the previously determined structure of the mouse Zfp57 DNA-binding domain in complex with DNA containing 5-methylcytosine (5mC), the side chains of Arg178 and Glu182 contact the methyl group via hydrophobic and van der Waals interactions. We examined the role of Glu182 in recognition of 5mC by mutagenesis. The majority of mutants examined lose selectivity of methylated (5mC) over unmodified (C) and oxidative derivatives, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine (5caC), suggesting that the side chain of Glu182 (the size and the charge) is dispensable for methyl group recognition but negatively impacts the binding of unmodified cytosine as well as oxidized derivatives of 5mC to achieve 5mC selectivity. Substitution of Glu182 with its corresponding amide (E182Q) had no effect on methylated DNA binding but gained significant binding affinity for 5caC DNA, resulting in a binding affinity for 5caC DNA comparable to that of the wild-type protein for 5mC. We show structurally that the uncharged amide group of E182Q interacts favorably with the carboxylate group of 5caC. Furthermore, introducing a positively charged arginine at position 182 resulted in a mutant (E182R) having higher selectivity for the negatively charged 5caC.

DNA Recognition of 5-Carboxylcytosine by a Zfp57 Mutant at an Atomic Resolution of 0.97 A,Liu Y, Olanrewaju YO, Zhang X, Cheng X Biochemistry. 2013 Nov 20. PMID:24236546^[4]

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

References

↑ Alonso MB, Zoidl G, Taveggia C, Bosse F, Zoidl C, Rahman M, Parmantier E, Dean CH, Harris BS, Wrabetz L, Muller HW, Jessen KR, Mirsky R. Identification and characterization of ZFP-57, a novel zinc finger transcription factor in the mammalian peripheral nervous system. J Biol Chem. 2004 Jun 11;279(24):25653-64. Epub 2004 Apr 7. PMID:15070898 doi:http://dx.doi.org/10.1074/jbc.M400415200
↑ Li X, Ito M, Zhou F, Youngson N, Zuo X, Leder P, Ferguson-Smith AC. A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints. Dev Cell. 2008 Oct;15(4):547-57. doi: 10.1016/j.devcel.2008.08.014. PMID:18854139 doi:http://dx.doi.org/10.1016/j.devcel.2008.08.014
↑ Liu Y, Toh H, Sasaki H, Zhang X, Cheng X. An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence. Genes Dev. 2012 Nov 1;26(21):2374-9. doi: 10.1101/gad.202200.112. Epub 2012 Oct, 11. PMID:23059534 doi:http://dx.doi.org/10.1101/gad.202200.112
↑ Liu Y, Olanrewaju YO, Zhang X, Cheng X. DNA Recognition of 5-Carboxylcytosine by a Zfp57 Mutant at an Atomic Resolution of 0.97 A Biochemistry. 2013 Nov 20. PMID:24236546 doi:http://dx.doi.org/10.1021/bi401360n

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4m9v"

@@ Line 1: / Line 1: @@
 ==Zfp57 mutant (E182Q) in complex with 5-carboxylcytosine DNA==
 <StructureSection load='4m9v' size='340' side='right' caption='[[4m9v]], [[Resolution|resolution]] 0.97&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gzn|4gzn]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Zfp57 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4m9v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m9v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m9v RCSB], [http://www.ebi.ac.uk/pdbsum/4m9v PDBsum]</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=4m9v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m9v OCA], [http://pdbe.org/4m9v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m9v RCSB], [http://www.ebi.ac.uk/pdbsum/4m9v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m9v ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4m9v" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4m9v

From Proteopedia

Revision as of 19:06, 4 August 2016

Zfp57 mutant (E182Q) in complex with 5-carboxylcytosine DNA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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