2qrv
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2qrv.jpg|left|200px]] | + | [[Image:2qrv.jpg|left|200px]] |
| - | + | ||
| - | '''Structure of Dnmt3a-Dnmt3L C-terminal domain complex''' | + | {{Structure |
| + | |PDB= 2qrv |SIZE=350|CAPTION= <scene name='initialview01'>2qrv</scene>, resolution 2.89Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= 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]) | ||
| + | }} | ||
| + | |||
| + | '''Structure of Dnmt3a-Dnmt3L C-terminal domain complex''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2QRV is a [ | + | 2QRV is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QRV OCA]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17713477 17713477] |
[[Category: DNA (cytosine-5-)-methyltransferase]] | [[Category: DNA (cytosine-5-)-methyltransferase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| Line 23: | Line 32: | ||
[[Category: transferase/transferase regulator complex]] | [[Category: transferase/transferase regulator complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:28:56 2008'' |
Revision as of 16:28, 20 March 2008
| |||||||
| , resolution 2.89Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | DNMT3A (Homo sapiens), DNMT3L (Homo sapiens) | ||||||
| Activity: | DNA (cytosine-5-)-methyltransferase, with EC number 2.1.1.37 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of Dnmt3a-Dnmt3L C-terminal domain complex
Overview
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.
About this Structure
2QRV is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Mar 20 18:28:56 2008
