生物
蛋白质亚单位
低温电子显微
核糖核酸
N6-甲基腺苷
结合位点
生物化学
细胞生物学
计算生物学
生物物理学
甲基转移酶
DNA
基因
甲基化
作者
Shichen Su,Shanshan Li,Ting Deng,Minsong Gao,Yue Yin,Baixing Wu,Chao Peng,Jianzhao Liu,Jinbiao Ma,Kaiming Zhang
标识
DOI:10.1038/s41422-022-00725-8
摘要
N6-methyladenosine (m6A) is the most abundant ribonucleotide modification among eukaryotic messenger RNAs. The m6A "writer" consists of the catalytic subunit m6A-METTL complex (MAC) and the regulatory subunit m6A-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 m6A writer complex, in which MACOM binds to MAC mainly through WTAP and METTL3 interactions. In combination with in vitro RNA substrate binding and m6A methyltransferase activity assays, our results illustrate the molecular basis of how MACOM assembles and interacts with MAC to form an active m6A writer complex.
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