SETD3 is an actin histidine methyltransferase that prevents primary dystocia.

ABSTRACT: For more than 50 years, the methylation of mammalian actin at histidine 73 has been known to occur¹. Despite the pervasiveness of His73 methylation, which we find is conserved in several model animals and plants, its function remains unclear and the enzyme that generates this modification is unknown. Here we identify SET domain protein 3 (SETD3) as the physiological actin His73 methyltransferase. Structural studies reveal that an extensive network of interactions clamps the actin peptide onto the surface of SETD3 to orient His73 correctly within the catalytic pocket and to facilitate methyl transfer. His73 methylation reduces the nucleotide-exchange rate on actin monomers and modestly accelerates the assembly of actin filaments. Mice that lack SETD3 show complete loss of actin H

SUBMITTER: Wilkinson AW 

PROVIDER: S-EPMC6511263 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature