Searching for the pHis readers with chemical tools

Abstract

Phosphorylation is one of the most studied post-translational modifications (PTMs), related to cell signaling, gene expression, differentiation, and other biological mechanisms. Phosphorylation affects diverse physiological functions through kinases (writers), phosphatases (erasers), and readers or acceptors which recognize the phosphorylation marks. Due to their roles in vivo, these proteins are attractive drug targets. Among the phosphorylations, phosphohistidine (pHis) is an underexplored PTM. Unlike the P-O bonds in the phosphoesters of Ser, Thr, and Tyr, the P-N bond in pHis is much less stable, making conventional methods incompatible with pHis research. While recent technological development enabled the identification of pHis sites and their functional investigations, studies to find the kinase, phosphatase, and reader related to pHis have been scarcely reported. Here, we report our progress in discovering the pHis readers and acceptors. This study will be the basis of identifying novel roles of this PTM.