9BAP

CryoEM structure of Apo-DIM2

Summary for 9BAP

• Entry DOI: 10.2210/pdb9bap/pdb
• EMDB information: 44410
• Descriptor: DNA (cytosine-5-)-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE, ZINC ION (3 entities in total)
• Functional Keywords: dna methyltransferase, transferase
• Biological source: Neurospora crassa
• Total number of polymer chains: 1
• Total formula weight: 162802.46

Authors

Song, J.,Shao, Z. (deposition date: 2024-04-04, release date: 2024-07-24, Last modification date: 2025-02-05)

Primary citation

Shao, Z.,Lu, J.,Khudaverdyan, N.,Song, J.
Multi-layered heterochromatin interaction as a switch for DIM2-mediated DNA methylation.
Nat Commun, 15:6815-6815, 2024

PubMed Abstract: Functional crosstalk between DNA methylation, histone H3 lysine-9 trimethylation (H3K9me3) and heterochromatin protein 1 (HP1) is essential for proper heterochromatin assembly and genome stability. However, how repressive chromatin cues guide DNA methyltransferases for region-specific DNA methylation remains largely unknown. Here, we report structure-function characterizations of DNA methyltransferase Defective-In-Methylation-2 (DIM2) in Neurospora. The DNA methylation activity of DIM2 requires the presence of both H3K9me3 and HP1. Our structural study reveals a bipartite DIM2-HP1 interaction, leading to a disorder-to-order transition of the DIM2 target-recognition domain that is essential for substrate binding. Furthermore, the structure of DIM2-HP1-H3K9me3-DNA complex reveals a substrate-binding mechanism distinct from that for its mammalian orthologue DNMT1. In addition, the dual recognition of H3K9me3 peptide by the DIM2 RFTS and BAH1 domains allosterically impacts the DIM2-substrate binding, thereby controlling DIM2-mediated DNA methylation. Together, this study uncovers how multiple heterochromatin factors coordinately orchestrate an activity-switching mechanism for region-specific DNA methylation.

PubMed: 39122718
DOI: 10.1038/s41467-024-51246-4

Experimental method

ELECTRON MICROSCOPY (2.88 Å)