7o45

Crystal structure of ADD domain of the human DNMT3B methyltransferase

spinqualitylabelsall models 7o45, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7o45 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: BR, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease DNM3B_HUMAN ICF syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function DNM3B_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. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing (By similarity). In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. Function as transcriptional corepressor by associating with ZHX1. Publication Abstract from PubMed De novo DNA methylation in early mammalian development depends on the activity of the DNMT3 methyltransferase family. An autoinhibitory mechanism involving the interaction between ADD and the catalytic domains of DNMT3A has been described. ADD is a zinc-coordinating histone-binding domain. The ADD domain of DNMT3A, when bound to a K4-unmethylated histone H3 tail, switches the enzyme to its catalytically active state. DNMT3B is another de novo methyltransferase enzyme with a more strict tissue- and stage-specific expression profile and a slightly different site specificity, lacking cooperative DNA methylation activity. Here, we obtained the crystal structure of the DNMT3B ADD domain, which demonstrated the extended conformation of the autoinhibitory loop even in the absence of the histone H3 tail. The lack of interaction between DNMT3B ADD and the methyltransferase domain was confirmed using an in vitro pull-down assay. The structural rearrangements in the loop also created an additional protein interaction interface leading to the formation of trimers in crystal, which may reflect their possible involvement in some unknown protein-protein interactions. Our results suggest that DNMT3B, in contrast to DNMT3A, has different modes of regulation of its activity that are independent of H3K4 methylation status. Structure of the DNMT3B ADD domain suggests the absence of a DNMT3A-like autoinhibitory mechanism.,Boyko K, Arkova O, Nikolaeva A, Popov VO, Georgiev P, Bonchuk A Biochem Biophys Res Commun. 2022 Sep 3;619:124-129. doi:, 10.1016/j.bbrc.2022.06.036. Epub 2022 Jun 18. PMID:35760008 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA methyltransferase 3D structures

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