Proteinadenylyl

Proteinadenylyl, commonly referred to as AMPylation or adenylylation, is a post-translational modification in which an adenosine monophosphate (AMP) moiety is covalently attached to a protein substrate. The reaction is carried out by protein adenylyltransferases (PATs), which typically transfer AMP from ATP to nucleophilic side chains on target amino acids, most often serine, threonine, or tyrosine, though other residues can be modified in certain contexts. The modification can alter enzyme activity, protein interactions, stability, or subcellular localization, thereby regulating cellular signaling pathways.

Two major classes of enzymes mediate protein adenylylation. Fic-domain proteins constitute a widespread family characterized by the conserved HPFxxG motif and an active-site histidine essential for catalysis; these enzymes can either activate or inhibit substrates depending on context. Non-Fic adenylyltransferases also exist and contribute to the diversity of AMP-transfer reactions. In bacteria, AMPylation is a notable virulence mechanism, used to manipulate host cell processes during infection. Examples include Legionella pneumophila SidM/DrrA, which AMPylates Rab1 to control vesicle trafficking, and other toxins that AMPylate Rho-family GTPases, affecting the cytoskeleton.

Reversibility is observed in some systems, with specific de-AMPylases capable of removing the AMP group and restoring the substrate’s previous state, enabling dynamic regulation of signaling networks. Detection and study rely on mass spectrometry, AMP-specific probes, and biochemical assays to identify modified proteins and map modification sites.

See also: AMPylation; Fic-domain proteins; de-AMPylation; SidM/DrrA; DupA/DupB; Legionella.