Molecular basis for histidine N3-specific methylation of actin H73 by SETD3
Yihui Zheng, Xingrun Zhang, Haitao Li
Abstract
As an extension of the central dogma, dynamic modifications of macromolecules play a key role in shaping cellular traits through modulating diverse cellular processes, such as gene regulation and signaling. In addition to lysine and arginine methylations that have been widely characterized in histone 1 as well as nonhistone proteins 2 , histidine methylation stands out as another important type of protein/peptide methylation for biological regulation. Remarkably, histidine methylation could occur to N1 or N3 position of its imidazole ring, posing an interesting topic to understand the biology underlying position-specific methylation of histidine. Previously, we have revealed the structural basis for histidine N1-specific methylation by human CARNMT1 3 . Recently, SET domain-containing protein 3 (SETD3) was identified as an N3-specific histidine methyltransferase of β-actin at the highly conserved residue H73 4 , 5 . Functionally, N3 methylation of H73 is associated with actin polymerization and ATP hydrolysis 6 , 7 , 8 , highlighting a role of histidine methylation in regulating cell motility.