7VF2

Human m6A-METTL associated complex (WTAP, VIRMA, ZC3H13, and HAKAI)

7VF2 の概要

• エントリーDOI: 10.2210/pdb7vf2/pdb
• EMDBエントリー: 31946
• 分子名称: Protein virilizer homolog, Zinc finger CCCH domain-containing protein 13, Pre-mRNA-splicing regulator WTAP (3 entities in total)
• 機能のキーワード: m6a-mettl associated complex, cryo-em, wtap, virma., rna binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 355109.35

構造登録者

Su, S.,Li, S.,Deng, T.,Gao, M.,Yin, Y.,Wu, B.,Peng, C.,Liu, J.,Ma, J.,Zhang, K. (登録日: 2021-09-10, 公開日: 2022-09-14, 最終更新日: 2025-07-02)

主引用文献

Su, S.,Li, S.,Deng, T.,Gao, M.,Yin, Y.,Wu, B.,Peng, C.,Liu, J.,Ma, J.,Zhang, K.
Cryo-EM structures of human m6A writer complexes.
Cell Res., 32:982-994, 2022

PubMed Abstract: N-methyladenosine (mA) is the most abundant ribonucleotide modification among eukaryotic messenger RNAs. The mA "writer" consists of the catalytic subunit mA-METTL complex (MAC) and the regulatory subunit mA-METTL-associated complex (MACOM), the latter being essential for enzymatic activity. Here, we report the cryo-electron microscopy (cryo-EM) structures of MACOM at a 3.0-Å resolution, uncovering that WTAP and VIRMA form the core structure of MACOM and that ZC3H13 stretches the conformation by binding VIRMA. Furthermore, the 4.4-Å resolution cryo-EM map of the MACOM-MAC complex, combined with crosslinking mass spectrometry and GST pull-down analysis, elucidates a plausible model of the mA writer complex, in which MACOM binds to MAC mainly through WTAP and METTL3 interactions. In combination with in vitro RNA substrate binding and mA methyltransferase activity assays, our results illustrate the molecular basis of how MACOM assembles and interacts with MAC to form an active mA writer complex.

PubMed: 36167981
DOI: 10.1038/s41422-022-00725-8

実験手法

ELECTRON MICROSCOPY (3 Å)