Post-translational modifications play important roles in mediating protein functions in a wide variety of cellular events in vivo. HEMK2–TRMT112 heterodimer has been reported to be responsible for both histone lysine methylation and eukaryotic release factor 1 (eRF1) glutamine methylation. However, how HEMK2–TRMT112 complex recognizes and catalyzes eRF1 glutamine methylation is largely unknown. Here, we present two structures of HEMK2–TRMT112, with one bound to SAM and the other bound with SAH and methylglutamine (Qme). Structural analyses of the post-catalytic complex, complemented by mass spectrometry experiments, indicate that the HEMK2 utilizes a specific pocket to accommodate the substrate glutamine and catalyzes the subsequent methylation. Therefore, our work not only throws light on the protein glutamine methylation mechanism, but also reveals the dual activity of HEMK2 by catalyzing the methylation of both Lys and Gln residues.
Structural insight into HEMK2–TRMT112-mediated glutamine methylation
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Jie Gao, Bin Wang, Huijuan Yu, Gao Wu, Cuihong Wan, Wenting Liu, Shanhui Liao, Liansheng Cheng, Zhongliang Zhu; Structural insight into HEMK2–TRMT112-mediated glutamine methylation. Biochem J 16 October 2020; 477 (19): 3833–3838. doi: https://doi.org/10.1042/BCJ20200594
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