8tci | pdb_00008tci

Crystal structure of DNMT3C-DNMT3L in complex with CGG DNA

spinqualitylabelsall models 8tci, resolution 3.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8tci is a 6 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.19Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DNM3C_MOUSE DNA methyltransferase that specifically methylates the promoters of evolutionarily young retrotransposons in the male germline (PubMed:27856912, PubMed:28854222). De novo methylation and subsequent repression of transposable elements prevents their mobilization, which is essential for germline integrity (PubMed:27856912, PubMed:28854222). Publication Abstract from PubMed DNA methylation is one of the major epigenetic mechanisms crucial for gene regulation and genome stability. De novo DNA methyltransferase DNMT3C is required for silencing evolutionarily young transposons during mice spermatogenesis. Mutation of DNMT3C led to a sterility phenotype that cannot be rescued by its homologues DNMT3A and DNMT3B. However, the structural basis of DNMT3C-mediated DNA methylation remains unknown. Here, we report the structure and mechanism of DNMT3C-mediated DNA methylation. The DNMT3C methyltransferase domain recognizes CpG-containing DNA in a manner similar to that of DNMT3A and DNMT3B, in line with their high sequence similarity. However, two evolutionary covariation sites, C543 and E590, diversify the substrate interaction among DNMT3C, DNMT3A and DNMT3B, resulting in distinct DNA methylation activity and specificity between DNMT3C, DNMT3A and DNMT3B in vitro. In addition, our combined structural and biochemical analysis reveals that the disease-causing rahu mutation of DNMT3C compromises its oligomerization and DNA-binding activities, providing an explanation for the loss of DNA methylation activity caused by this mutation. This study provides a mechanistic insight into DNMT3C-mediated DNA methylation that complements DNMT3A- and DNMT3B-mediated DNA methylation in mice, unravelling a regulatory mechanism by which evolutionary conservation and diversification fine-tunes the activity of de novo DNA methyltransferases. The structure of DNA methyltransferase DNMT3C reveals an activity-tuning mechanism for DNA methylation.,Khudaverdyan N, Lu J, Chen X, Herle G, Song J J Biol Chem. 2024 Aug 2:107633. doi: 10.1016/j.jbc.2024.107633. PMID:39098534 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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