Spray-type modifications: an emerging paradigm in post-translational modifications

Recent and intriguing research demonstrates that post-translational modification (PTM) events can act in a local-dependent manner in addition to the traditional sequence-dependent manner.We propose the spray-type PTM concept and describe a mechanism that focuses on the exposure level of reactive electrophilic substrate molecules at the active sites of PTM enzymes.Spray-type PTMs involve chemical interactions between electrophilic groups and nucleophilic moieties that are in close proximity, resembling the principles behind contemporary proximity labeling techniques.We further propose that spray-type PTMs play crucial roles in the simultaneous regulation of proteins within the same location, which are crucial for efficient responses to various stressors such as DNA breaks, heat shock stress, or viral infection. A post-translational modification (PTM) occurs when a nucleophilic residue (e.g., lysine of a target protein) attacks electrophilic substrate molecules (e.g., acyl-AMP), involving writer enzymes or even occurring spontaneously. Traditionally, this phenomenon was thought to be sequence specific; however, recent research suggests that PTMs can also occur in a non-sequence-specific manner confined to a specific location in a cell. In this Opinion, we compile the accumulated evidence of spray-type PTMs and propose a mechanism for this phenomenon based on the exposure level of reactive electrophilic substrate molecules at the active site of the PTM writers. Overall, a spray-type PTM conceptual framework is useful for comprehending the promiscuous PTM writer events that cannot be adequately explained by the traditional concept of sequence-dependent PTM events. A post-translational modification (PTM) occurs when a nucleophilic residue (e.g., lysine of a target protein) attacks electrophilic substrate molecules (e.g., acyl-AMP), involving writer enzymes or even occurring spontaneously. Traditionally, this phenomenon was thought to be sequence specific; however, recent research suggests that PTMs can also occur in a non-sequence-specific manner confined to a specific location in a cell. In this Opinion, we compile the accumulated evidence of spray-type PTMs and propose a mechanism for this phenomenon based on the exposure level of reactive electrophilic substrate molecules at the active site of the PTM writers. Overall, a spray-type PTM conceptual framework is useful for comprehending the promiscuous PTM writer events that cannot be adequately explained by th