7YI9

Cryo-EM structure of SAM-bound MTA1-MTA9-p1-p2 complex

Summary for 7YI9

• Entry DOI: 10.2210/pdb7yi9/pdb
• EMDB information: 33854
• Descriptor: MTA9, MT-a70 family protein, P1, ... (5 entities in total)
• Functional Keywords: n6-adenine methylation, mtac holoenzyme, dna binding protein
• Biological source: Tetrahymena thermophila SB210; More
• Total number of polymer chains: 4
• Total formula weight: 156610.18

Authors

Yan, J.J.,Guan, Z.Y.,Liu, F.Q.,Yan, X.H.,Hou, M.J.,Yin, P. (deposition date: 2022-07-15, release date: 2023-01-18, Last modification date: 2025-07-02)

Primary citation

Yan, J.,Liu, F.,Guan, Z.,Yan, X.,Jin, X.,Wang, Q.,Wang, Z.,Yan, J.,Zhang, D.,Liu, Z.,Wu, S.,Yin, P.
Structural insights into DNA N 6 -adenine methylation by the MTA1 complex.
Cell Discov, 9:8-8, 2023

PubMed Abstract: N-methyldeoxyadenine (6mA) has recently been reported as a prevalent DNA modification in eukaryotes. The Tetrahymena thermophila MTA1 complex consisting of four subunits, namely MTA1, MTA9, p1, and p2, is the first identified eukaryotic 6mA methyltransferase (MTase) complex. Unlike the prokaryotic 6mA MTases which have been biochemically and structurally characterized, the operation mode of the MTA1 complex remains largely elusive. Here, we report the cryogenic electron microscopy structures of the quaternary MTA1 complex in S-adenosyl methionine (SAM)-bound (2.6 Å) and S-adenosyl homocysteine (SAH)-bound (2.8 Å) states. Using an AI-empowered integrative approach based on AlphaFold prediction and chemical cross-linking mass spectrometry, we further modeled a near-complete structure of the quaternary complex. Coupled with biochemical characterization, we revealed that MTA1 serves as the catalytic core, MTA1, MTA9, and p1 likely accommodate the substrate DNA, and p2 may facilitate the stabilization of MTA1. These results together offer insights into the molecular mechanism underpinning methylation by the MTA1 complex and the potential diversification of MTases for N-adenine methylation.

PubMed: 36658132
DOI: 10.1038/s41421-022-00516-w

Experimental method

ELECTRON MICROSCOPY (2.6 Å)