Carbamylated LL-37 as a modulator of the immune response.


Journal Article

Carbamylation of lysine residues and protein N-termini is an ubiquitous, non-enzymatic post-translational modification. Carbamylation at sites of inflammation is due to cyanate formation during the neutrophil oxidative burst and may target lysine residues within the antimicrobial peptide LL-37. The bactericidal and immunomodulatory properties of LL-37 depend on its secondary structure and cationic nature, which are conferred by arginine and lysine residues. Therefore, carbamylation may affect the biological functions of LL-37. The present study examined the kinetics and pattern of LL-37 carbamylation to investigate how this modification affects the bactericidal, cytotoxic and immunomodulatory function of the peptide. The results indicated that LL-37 undergoes rapid modification in the presence of physiological concentrations of cyanate, yielding a spectrum of diverse carbamylated peptides. Mass spectrometry analyses revealed that theN-terminal amino group of Leu-1 was highly reactive and was modified almost instantly by cyanate to generate the predominant form of the modified peptide, named LL-37(C1) This was followed by the sequential carbamylation of Lys-8, Lys-12, and Lys-15 to yield LL-37(C8), and Lys-15 to yield LL-37(C12,15) Carbamylation had profound and diverse effects on the structure and biological properties of LL-37. In some cases, anti-inflammatory LL-37 was rapidly converted to pro-inflammatory LL-37.

Full Text

Cited Authors

  • Koro, C; Hellvard, A; Delaleu, N; Binder, V; Scavenius, C; Bergum, B; Główczyk, I; Roberts, HM; Chapple, ILC; Grant, MM; Rapala-Kozik, M; Klaga, K; Enghild, JJ; Potempa, J; Mydel, P

Published Date

  • April 2016

Published In

Volume / Issue

  • 22 / 3

Start / End Page

  • 218 - 229

PubMed ID

  • 26878866

Pubmed Central ID

  • 26878866

Electronic International Standard Serial Number (EISSN)

  • 1753-4267

International Standard Serial Number (ISSN)

  • 1753-4259

Digital Object Identifier (DOI)

  • 10.1177/1753425916631404


  • eng