An asparagine/glycine switch governs product specificity of human N-terminal methyltransferase NTMT2

作者：Dong, Cheng; Dong, Guangping; Li, Li; Zhu, Licheng; Tempel, Wolfram; Liu, Yanli; Huang, Rong^*; Min, Jinrong^*

来源：Communications Biology, 2018, 1(1): 183.

DOI：10.1038/s42003-018-0196-2

• HISTONE METHYLATION
• STRUCTURAL BASIS
• CENP-A
• IDENTIFICATION
• INTEGRATION
• REFINEMENT
• MECHANISM
• BINDING
• MODEL
• NRMT

alpha-N-terminal methylation of proteins is an important post-translational modification that is catalyzed by two different N-terminal methyltransferases, namely NTMT1 and NTMT2. Previous studies have suggested that NTMT1 is a tri-methyltransferase, whereas NTMT2 is a mono-methyltransferase. Here, we report the first crystal structures, to our knowledge, of NTMT2 in binary complex with S-adenosyl-L-methionine as well as in ternary complex with Sadenosyl-L-homocysteine and a substrate peptide. Our structural observations combined with biochemical studies reveal that NTMT2 is also able to di-/tri-methylate the GPKRIA peptide and di-methylate the PPKRIA peptide, otherwise it is predominantly a mono-methyltransferase. The residue N89 of NTMT2 serves as a gatekeeper residue that regulates the binding of unmethylated versus monomethylated substrate peptide. Structural comparison of NTMT1 and NTMT2 prompts us to design a N89G mutant of NTMT2 that can profoundly alter its catalytic activities and product specificities.

• 出版日期2018
• 单位井冈山大学