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2qrv

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Revision as of 01:43, 12 September 2015

Structure of Dnmt3a-Dnmt3L C-terminal domain complex

Structural highlights

2qrv is a 8 chain structure with sequence from Human. The July 2011 RCSB PDB Molecule of the Month feature on DNA Methylases by David Goodsell is 10.2210/rcsb_pdb/mom_2011_7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2pv0, 2pvc
Gene:	DNMT3A (HUMAN), DNMT3L (HUMAN)
Activity:	DNA (cytosine-5-)-methyltransferase, with EC number 2.1.1.37
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[DNM3A_HUMAN] Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZNF238. Can actively repress transcription through the recruitment of HDAC activity (By similarity).^[1] [DNM3L_HUMAN] Catalytically inactive regulatory factor of DNA methyltransferases. It is essential for the function of DNMT3A and DNMT3B. Activates DNMT3A and DNMT3B by binding to their catalytic domain. Accelerates the binding of DNA and AdoMet to the methyltransferases and dissociates from the complex after DNA binding to the methyltransferases. Recognizes unmethylated histone H3 lysine 4 (H3K4) and induces de novo DNA methylation by recruitment or activation of DNMT3.^[2]

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

Genetic imprinting, found in flowering plants and placental mammals, uses DNA methylation to yield gene expression that is dependent on the parent of origin. DNA methyltransferase 3a (Dnmt3a) and its regulatory factor, DNA methyltransferase 3-like protein (Dnmt3L), are both required for the de novo DNA methylation of imprinted genes in mammalian germ cells. Dnmt3L interacts specifically with unmethylated lysine 4 of histone H3 through its amino-terminal PHD (plant homeodomain)-like domain. Here we show, with the use of crystallography, that the carboxy-terminal domain of human Dnmt3L interacts with the catalytic domain of Dnmt3a, demonstrating that Dnmt3L has dual functions of binding the unmethylated histone tail and activating DNA methyltransferase. The complexed C-terminal domains of Dnmt3a and Dnmt3L showed further dimerization through Dnmt3a-Dnmt3a interaction, forming a tetrameric complex with two active sites. Substitution of key non-catalytic residues at the Dnmt3a-Dnmt3L interface or the Dnmt3a-Dnmt3a interface eliminated enzymatic activity. Molecular modelling of a DNA-Dnmt3a dimer indicated that the two active sites are separated by about one DNA helical turn. The C-terminal domain of Dnmt3a oligomerizes on DNA to form a nucleoprotein filament. A periodicity in the activity of Dnmt3a on long DNA revealed a correlation of methylated CpG sites at distances of eight to ten base pairs, indicating that oligomerization leads Dnmt3a to methylate DNA in a periodic pattern. A similar periodicity is observed for the frequency of CpG sites in the differentially methylated regions of 12 maternally imprinted mouse genes. These results suggest a basis for the recognition and methylation of differentially methylated regions in imprinted genes, involving the detection of both nucleosome modification and CpG spacing.

Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation.,Jia D, Jurkowska RZ, Zhang X, Jeltsch A, Cheng X Nature. 2007 Sep 13;449(7159):248-51. Epub 2007 Aug 22. PMID:17713477^[3]

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

References

↑ Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden JM, Bollen M, Esteller M, Di Croce L, de Launoit Y, Fuks F. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006 Feb 16;439(7078):871-4. Epub 2005 Dec 14. PMID:16357870 doi:10.1038/nature04431
↑ Ooi SK, Qiu C, Bernstein E, Li K, Jia D, Yang Z, Erdjument-Bromage H, Tempst P, Lin SP, Allis CD, Cheng X, Bestor TH. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature. 2007 Aug 9;448(7154):714-7. PMID:17687327 doi:http://dx.doi.org/10.1038/nature05987
↑ Jia D, Jurkowska RZ, Zhang X, Jeltsch A, Cheng X. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature. 2007 Sep 13;449(7159):248-51. Epub 2007 Aug 22. PMID:17713477 doi:10.1038/nature06146

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2qrv"

@@ Line 2: / Line 2: @@
 <StructureSection load='2qrv' size='340' side='right' caption='[[2qrv]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2qrv]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The July 2011 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''DNA Methylases''  by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2011_7 10.2210/rcsb_pdb/mom_2011_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QRV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QRV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2qrv]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. The July 2011 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''DNA Methylases''  by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2011_7 10.2210/rcsb_pdb/mom_2011_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QRV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QRV FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2pv0|2pv0]], [[2pvc|2pvc]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DNMT3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), DNMT3L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DNMT3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DNMT3L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_(cytosine-5-)-methyltransferase DNA (cytosine-5-)-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.37 2.1.1.37] </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=2qrv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qrv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2qrv RCSB], [http://www.ebi.ac.uk/pdbsum/2qrv 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=2qrv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qrv OCA], [http://pdbe.org/2qrv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qrv RCSB], [http://www.ebi.ac.uk/pdbsum/2qrv PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2qrv" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 37: / Line 38: @@
 </StructureSection>
 [[Category: DNA Methylases]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: RCSB PDB Molecule of the Month]]
 [[Category: Cheng, X]]

2qrv

From Proteopedia

Revision as of 01:43, 12 September 2015

Structure of Dnmt3a-Dnmt3L C-terminal domain complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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