Ying Meng, Zhouxian Li, Ming He, Quanqing Zhang, Youchao Deng, Yinsheng Wang, Rong Huang
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引用次数: 0
Abstract
α-N-Methylation (Nα-methylation), catalyzed by protein N-terminal methyltransferases (NTMTs), constitutes a crucial post-translational modification involving the transfer of a methyl group from S-adenosyl-l-methionine (SAM) to the Nα-terminal amino group of substrate proteins. NTMT1/2 are known to methylate canonical Nα sequences, such as X–P-K/R. With over 300 potential human protein substrates, only a small fraction has been validated, and even less is known about the functions of Nα-methylation. This study delves into the characterizations of protein arginine deiminase 1 (PAD1) as a substrate of NTMT1. By employing biochemical and cellular assays, we demonstrated NTMT1-mediated Nα-methylation of PAD1, leading to an increase in protein half-life and the modulation of protein–protein interactions in HEK293T cells. The methylation of PAD1 appears nonessential to its enzymatic activity or cellular localization. Proteomic studies revealed differential protein interactions between unmethylated and Nα-methylated PAD1, suggesting a regulatory role for Nα-methylation in modulating PAD1’s protein–protein interactions. These findings shed light on the intricate molecular mechanisms governing PAD1 function and expand our knowledge of Nα-methylation in regulating protein function.
期刊介绍:
Journal of Proteome Research publishes content encompassing all aspects of global protein analysis and function, including the dynamic aspects of genomics, spatio-temporal proteomics, metabonomics and metabolomics, clinical and agricultural proteomics, as well as advances in methodology including bioinformatics. The theme and emphasis is on a multidisciplinary approach to the life sciences through the synergy between the different types of "omics".