9U92

Cryo-EM structure of Tetrahymena DNA methyltransferase complex MTA1c

Summary for 9U92

• Entry DOI: 10.2210/pdb9u92/pdb
• EMDB information: 63956
• Descriptor: MT-a70 family protein, MT-a70 family protein MTA9, Myb-like DNA-binding domain protein, ... (5 entities in total)
• Functional Keywords: dna methyltransferase, dna n6-methyladenine modification, protein-dna complex, chromatin regulation, gene regulation, dna binding protein
• Biological source: Tetrahymena thermophila SB210; More
• Total number of polymer chains: 4
• Total formula weight: 158323.87

Authors

Xu, Q.,Shi, Z.B. (deposition date: 2025-03-26, release date: 2025-11-05)

Primary citation

Xu, Q.,Xie, Y.,Shi, Z.
Mechanism for the substrate recognition by a eukaryotic DNA N 6 -adenine methyltransferase complex.
Nat Commun, 16:8690-8690, 2025

PubMed Abstract: In eukaryotes, DNA N-methyladenine (6mA) modification plays important roles in various cellular functions, such as chromatin dynamics, gene expression regulation, and DNA damage response. It remains largely unknown how eukaryotic DNA 6mA methyltransferases (MTases) recognize their substrates. Here, we reported the structures of DNA-bound eukaryotic 6mA MTase complexes. The MTA1 complex (MTA1c) in ciliates is composed of MTA1, MTA9 (or MTA9-B), p1 and p2 subunits. Cryo-electron microscopy structures of MTA1c-DNA complexes reveal that DNA lies on the surface of the MTA1-MTA9/9-B dimer and is clamped by the p1 N-terminal region. The target deoxyadenosine is flipped out of the DNA duplex and approaches the catalytic center. Unmethylated and hemi-methylated DNA substrates bind MTA1c with differential conformational dynamics. Our structural and biochemical studies shed light on the activation and substrate recognition of MTA1c and provide a framework for understanding the molecular mechanism of DNA 6mA modification in eukaryotes.

PubMed: 41027852
DOI: 10.1038/s41467-025-63738-y

Experimental method

ELECTRON MICROSCOPY (2.68 Å)