7YI8

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

7YI8 の概要

• エントリーDOI: 10.2210/pdb7yi8/pdb
• EMDBエントリー: 33853
• 分子名称: MTA9, MT-a70 family protein, P1, ... (5 entities in total)
• 機能のキーワード: n6-adenine methylation, mtac holoenzyme, dna binding protein
• 由来する生物種: Tetrahymena thermophila SB210; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 156596.15

構造登録者

Yan, J.J.,Guan, Z.Y.,Liu, F.Q.,Yan, X.H.,Hou, M.J.,Yin, P. (登録日: 2022-07-15, 公開日: 2023-01-18, 最終更新日: 2024-07-03)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.7 Å)