Bacterial FIC Proteins AMP Up Infection

Craig R. Roy^* and Shaeri Mukherjee

Section of Microbial Pathogenesis, School of Medicine, Yale University, 295 Congress Avenue, New Haven, CT 06536, USA.

Abstract: Proteins containing FIC (filamentation induced by cyclic adenosine monophosphate) domains are found in both prokaryotic and eukaryotic organisms, but their function has remained elusive. Recent studies indicate that bacterial FIC domain–containing proteins disrupt host cell processes after being delivered into eukaryotic host cells: The Vibrio parahaemolyticus VopS protein interferes with Rho guanine triphosphatase (GTPase) function, and the Legionella pneumophila AnkX protein disrupts the microtubule-dependent transport of vesicles. Analysis of the VopS protein revealed that the FIC domain covalently modifies Rac by transferring adenosine 5'-monophosphate (AMP) to a threonine residue in the switch 1 region of the protein. Thus, FIC domain–mediated AMPylation is involved in the posttranslational regulation of protein function, and this activity has been subverted by microbial pathogens to modulate cellular functions during infection.

* Corresponding author. Telephone, 203-737-2408; e-mail, craig.roy{at}yale.edu

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