Molecular basis for METTL9-mediated N1-histidine methylation

作者：Xiaoyang Wang, Huabin Xie, Qiong Guo, Dan Cao, Wenwen Ru, Shidong Zhao, Zhongliang Zhu, Jiahai Zhang, Wen Pan, Xuebiao Yao, Chao Xu · 发表于：Cell Discovery · 年份：2023 · DOI：10.1038/s41421-023-00548-w · 被引用次数：20 · 研究领域：Epigenetics and DNA Methylation、Cancer-related gene regulation、RNA modifications and cancer

Methylation is one of the most abundant and common posttranslational modifications (PTMs) and plays important roles in a wide range of cellular events 1 , 2 . Histidine methylation occurs at the N1 or N3 position of the imidazole ring and accounts for ~13% of protein methylation events 3 . Although methylhistidine was found in actin and myosin decades ago 4 , very few mammalian histidine-specific methyltransferases were identified until recently, and several groups identified SETD3 and METTL18 as actin and RPL3 histidine-N3 methyltransferases, respectively 5 , 6 , 7 , 8 , and METTL9 as a histidine-N1 methyltransferase 9 , 10 . Unlike SETD3 or METTL18, which methylates a unique substrate, METTL9 specifically recognizes an xHxH motif (H is for histidine and x denotes small residues.) and catalyzes the methylation of the second histidine. xHxH, as a known metal binding motif, is found in a wide range of metal binding proteins, suggesting the potential role of METTL9-dependent histidine methylation in mediating the metal binding capacities for those proteins. Despite its important role, the molecular mechanism underlying substrate recognition and methylation by METTL9 is largely unknown.