7VF5

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

Summary for 7VF5

• Entry DOI: 10.2210/pdb7vf5/pdb
• EMDB information: 31946 31947
• Descriptor: Protein virilizer homolog, Pre-mRNA-splicing regulator WTAP (2 entities in total)
• Functional Keywords: m6a-mettl associated complex, cryo-em, wtap, virma., rna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 290831.56

Authors

Su, S.,Li, S.,Deng, T.,Gao, M.,Yin, Y.,Wu, B.,Peng, C.,Liu, J.,Ma, J.,Zhang, K. (deposition date: 2021-09-10, release date: 2022-09-14, Last modification date: 2024-06-19)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3 Å)