NAD-dependent ADP-ribosylation of the Human Antimicrobial and Immune-Modulatory Peptide LL-37 by ADP-ribosyltransferase-1

Innate Immun. 2015 Apr;21(3):314-21. doi: 10.1177/1753425914536242. Epub 2014 Aug 15.

Abstract

LL-37 is a cationic peptide belonging to the cathelicidin family that has antimicrobial and immune-modulatory properties. Here we show that the mammalian mono-ADP-ribosyltransferase-1 (ART1), which selectively transfers the ADP-ribose moiety from NAD to arginine residues, ADP-ribosylates LL-37 in vitro. The incorporation of ADP-ribose was first observed by Western blot analysis and then confirmed by MALDI-TOF. Mass-spectrometry showed that up to four of the five arginine residues present in LL-37 could be ADP-ribosylated on the same peptide when incubated at a high NAD concentration in the presence of ART1. The attachment of negatively charged ADP-ribose moieties considerably alters the positive charge of the arginine residues thus reducing the cationicity of LL-37. The cationic nature of LL-37 is key for its ability to interact with cell membranes or negatively charged biomolecules, such as DNA, RNA, F-actin and glycosaminoglycans. Thus, the ADP-ribosylation of LL-37 is expected to have the potential to modulate LL-37 biological activities in several physiological and pathological settings.

Keywords: ADP-ribosylation; ART1; LL-37; NAD; cathelicidin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP Ribose Transferases / metabolism*
  • Adenosine Diphosphate Ribose / metabolism
  • Animals
  • Antimicrobial Cationic Peptides / metabolism*
  • Arginine / metabolism
  • Cell Line
  • Cell Membrane / metabolism
  • GPI-Linked Proteins / metabolism
  • Humans
  • Immunomodulation
  • Mass Spectrometry
  • NAD / metabolism*

Substances

  • Antimicrobial Cationic Peptides
  • GPI-Linked Proteins
  • NAD
  • CAP18 lipopolysaccharide-binding protein
  • Adenosine Diphosphate Ribose
  • Arginine
  • ADP Ribose Transferases
  • ART1 protein, human