7T02

Cryo-EM structure of DNMT5 pseudo-ternary complex solved by incubation with hemimethylated DNA and SAM

7T02 の概要

• エントリーDOI: 10.2210/pdb7t02/pdb
• 関連するPDBエントリー: 7R76 7R77 7R78
• EMDBエントリー: 25577
• 分子名称: DNA repair protein Rad8, DNA (5'-D(P*GP*TP*CP*AP*GP*(5CM)P*GP*CP*AP*TP*GP*G)-3'), DNA (5'-D(*CP*CP*AP*TP*GP*CP*GP*CP*TP*GP*AP*CP*A)-3'), ... (4 entities in total)
• 機能のキーワード: cytosine-5 methyltransferase, snf2 atpase, transferase, hemimethylated dna, transferase-dna complex, transferase/dna
• 由来する生物種: Cryptococcus neoformans var. grubii H99; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 286305.99

構造登録者

Wang, J.,Patel, D.J. (登録日: 2021-11-29, 公開日: 2022-02-23, 最終更新日: 2024-02-28)

主引用文献

Wang, J.,Catania, S.,Wang, C.,de la Cruz, M.J.,Rao, B.,Madhani, H.D.,Patel, D.J.
Structural insights into DNMT5-mediated ATP-dependent high-fidelity epigenome maintenance.
Mol.Cell, 82:1186-1198.e6, 2022

PubMed Abstract: Epigenetic evolution occurs over million-year timescales in Cryptococcus neoformans and is mediated by DNMT5, the first maintenance type cytosine methyltransferase identified in the fungal or protist kingdoms, the first dependent on adenosine triphosphate (ATP), and the most hemimethyl-DNA-specific enzyme known. To understand these novel properties, we solved cryo-EM structures of CnDNMT5 in three states. These studies reveal an elaborate allosteric cascade in which hemimethylated DNA binding first activates the SNF2 ATPase domain by a large rigid body rotation while the target cytosine partially flips out of the DNA duplex. ATP binding then triggers striking structural reconfigurations of the methyltransferase catalytic pocket to enable cofactor binding, completion of base flipping, and catalysis. Bound unmethylated DNA does not open the catalytic pocket and is instead ejected upon ATP binding, driving high fidelity. This unprecedented chaperone-like, enzyme-remodeling role of the SNF2 ATPase domain illuminates how energy is used to enable faithful epigenetic memory.

PubMed: 35202575
DOI: 10.1016/j.molcel.2022.01.028

実験手法

ELECTRON MICROSCOPY (3.8 Å)