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Carbamylated LL-37 as a modulator of the immune response.
- Source :
-
Innate Immunity . Apr2016, Vol. 22 Issue 3, p218-229. 12p. - Publication Year :
- 2016
-
Abstract
- 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 the N-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-37C1. This was followed by the sequential carbamylation of Lys-8, Lys-12, and Lys-15 to yield LL-37C8, and Lys-15 to yield LL-37C12,15. 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17534259
- Volume :
- 22
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Innate Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 113947365
- Full Text :
- https://doi.org/10.1177/1753425916631404