7R77

Cryo-EM structure of DNMT5 binary complex with hemimethylated DNA

7R77 の概要

• エントリーDOI: 10.2210/pdb7r77/pdb
• 関連するPDBエントリー: 7R76
• EMDBエントリー: 24292 24294
• 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'), ZINC ION, ... (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 serotype A (strain H99 / ATCC 208821 / CBS 10515 / FGSC 9487) (Filobasidiella neoformans var. grubii); 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: 2021-06-24, 公開日: 2022-02-23, 最終更新日: 2024-06-05)

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 Å)