title: NAD-dependent ADP-ribosylation of the human antimicrobial and immune-modulatory peptide LL-37 by ADP-ribosyltransferase-1.
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.
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy Department of Evolutionary Biology, University of Siena, Siena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Picchianti
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Russo
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Castagnini
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Biagini
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Soldaini
authors.affiliation: School of Biosciences and Biotechnologies, University of Camerino, Camerino, Italy enrico.balducci@unicam.it.
authors.forename: Enrico
authors.initials: E
authors.lastname: Balducci
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D013058:Mass Spectrometry; D009243:NAD / Q000378:metabolism*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D058851:GPI-Linked Proteins; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D001120:Arginine; D036002:ADP Ribose Transferases; C449301:ART1 protein, human; D054804:Cathelicidins
keywords: ADP-ribosylation; ART1; LL-37; NAD; cathelicidin