AMPylated

AMPylation, also known as adenylylation, is a post-translational modification in which an adenosine monophosphate (AMP) moiety is covalently attached to a substrate, typically a protein. The modification usually occurs on hydroxyl-containing residues such as serine, threonine, or tyrosine, and it can alter the substrate’s activity, interactions, localization, or stability by changing charge or conformation. AMPylation is catalyzed by AMP transferases, many of which possess a Fic domain, and ATP generally serves as the donor of the AMP group. The reaction is reversible; removal of AMP is called deAMPylation and is accomplished by specific hydrolases or, in some systems, by the same Fic-containing enzyme in a regulatory cycle.

In bacteria, AMPylation is employed by virulence factors to disrupt host cell signaling. Fic-domain effectors transfer AMP to host proteins, including small GTPases, thereby impairing cytoskeletal dynamics and immune responses to promote infection. In eukaryotes, AMPylation participates in normal cellular regulation. A well-studied example is the control of the endoplasmic reticulum chaperone BiP by the enzyme FICD (also known as HYPE), which can both AMPylate BiP to reduce its activity and deAMPylate BiP to restore function, depending on cellular conditions.

Detection and study of AMPylation rely on biochemical assays, mass spectrometry, and antibodies that recognize the AMP modification. Ongoing research seeks to map AMPylation networks across organisms and to understand how this modification interacts with other signaling pathways and cellular stress responses.