8EIH

Cryo-EM structure of human DNMT3B homo-tetramer (form I)

Summary for 8EIH

• Entry DOI: 10.2210/pdb8eih/pdb
• EMDB information: 28156 28157 28158 28159
• Descriptor: DNA (cytosine-5)-methyltransferase 3B, S-ADENOSYL-L-HOMOCYSTEINE, ZINC ION (3 entities in total)
• Functional Keywords: dna methyltransferase, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 5
• Total formula weight: 369823.84

Authors

Lu, J.W.,Song, J.K. (deposition date: 2022-09-15, release date: 2023-09-20, Last modification date: 2025-05-21)

Primary citation

Lu, J.,Fang, J.,Zhu, H.,Liang, K.L.,Khudaverdyan, N.,Song, J.
Structural basis for the allosteric regulation and dynamic assembly of DNMT3B.
Nucleic Acids Res., 51:12476-12491, 2023

PubMed Abstract: Oligomerization of DNMT3B, a mammalian de novo DNA methyltransferase, critically regulates its chromatin targeting and DNA methylation activities. However, how the N-terminal PWWP and ADD domains interplay with the C-terminal methyltransferase (MTase) domain in regulating the dynamic assembly of DNMT3B remains unclear. Here, we report the cryo-EM structure of DNMT3B under various oligomerization states. The ADD domain of DNMT3B interacts with the MTase domain to form an autoinhibitory conformation, resembling the previously observed DNMT3A autoinhibition. Our combined structural and biochemical study further identifies a role for the PWWP domain and its associated ICF mutation in the allosteric regulation of DNMT3B tetramer, and a differential functional impact on DNMT3B by potential ADD-H3K4me0 and PWWP-H3K36me3 bindings. In addition, our comparative structural analysis reveals a coupling between DNMT3B oligomerization and folding of its substrate-binding sites. Together, this study provides mechanistic insights into the allosteric regulation and dynamic assembly of DNMT3B.

PubMed: 37941146
DOI: 10.1093/nar/gkad972

Experimental method

ELECTRON MICROSCOPY (3.04 Å)