AMPylation – a new use for ATP
Post-translational modifications are key steps in the regulation of eukaryotic cell signaling. The modification of a protein can enhance or change the role of the protein. For instance, when a protein is phosphorylated, it might become an active enzyme, be targeted to a subcellular compartment or be efficiently degraded. In addition, the modified protein could act as a scaffold to cluster proteins and form signaling networks.
We recently discovered a bacterial virulence factor from Vibrio parahaemolyticus that mediates the modification of a conserved threonine residue on eukaryotic substrates via a phosphodiester bond with AMP (Yarbrough et al., Science 2009). This modification, called AMPylation, is mediated by a domain called a filamentation induced by cAMP (Fic) domain. We have solved the structure of VopS Fic domain and characterized the kinetics of AMPylation (Luong et al., J Biol Chem 2010).
As Fic domains are evolutionarily conserved in bacteria as well as higher organisms and evidence has been found for AMPylation occurring in lysates from human tissue culture cells, we are currently studying the role of this post-translational modification in eukaryotes. To accomplish this, we are developing tools to detect specific AMPylation, including an antibody against AMPylated threonine (Hao et al., J Biotechnol 2011).
Publications on AMPylation