Structural and Functional Consequences Induced by Post-Translational Modifications in α-Defensins

Abstract EN

HNP-1 is an antimicrobial peptide that undergoes proteolytic cleavage to become a mature peptide.

This process represents the mechanism commonly used by the cells to obtain a fully active antimicrobial peptide.

In addition, it has been recently described that HNP-1 is recognized as substrate by the arginine-specific ADP-ribosyltransferase-1.

Arginine-specific mono-ADP-ribosylation is an enzyme-catalyzed post-translational modification in which NAD+ serves as donor of the ADP-ribose moiety, which is transferred to the guanidino group of arginines in target proteins.

While the arginine carries one positive charge, the ADP-ribose is negatively charged at the phosphate moieties at physiological pH.

Therefore, the attachment of one or more ADP-ribose units results in a marked change of cationicity.

ADP-ribosylation of HNP-1 drastically reduces its cytotoxic and antibacterial activities.

While the chemotactic activity of HNP-1 remains unaltered, its ability to induce interleukin-8 production is enhanced.

The arginine 14 of HNP-1 modified by the ADP-ribose is in some cases processed into ornithine, perhaps representing a different modality in the regulation of HNP-1 activities.