7O45
Crystal structure of ADD domain of the human DNMT3B methyltransferase
Summary for 7O45
| Entry DOI | 10.2210/pdb7o45/pdb |
| Descriptor | Isoform 6 of DNA (cytosine-5)-methyltransferase 3B, ZINC ION, BROMIDE ION, ... (4 entities in total) |
| Functional Keywords | methyltransferase 3b, dna methylation, dnmt3b, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 4 |
| Total formula weight | 67251.37 |
| Authors | Boyko, K.M.,Nikolaeva, A.Y.,Bonchuk, A.N.,Georgiev, P.G.,Popov, V.O. (deposition date: 2021-04-05, release date: 2022-04-13, Last modification date: 2024-01-31) |
| Primary citation | Boyko, K.,Arkova, O.,Nikolaeva, A.,Popov, V.O.,Georgiev, P.,Bonchuk, A. Structure of the DNMT3B ADD domain suggests the absence of a DNMT3A-like autoinhibitory mechanism. Biochem.Biophys.Res.Commun., 619:124-129, 2022 Cited by PubMed Abstract: 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. PubMed: 35760008DOI: 10.1016/j.bbrc.2022.06.036 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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