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Lipopolysaccharide bound structures of the active fragments of fowlicidin‐1, a cathelicidin family of antimicrobial and antiendotoxic peptide from chicken, determined by transferred nuclear overhauser effect spectroscopy
Author(s) -
Bhunia Anirban,
Mohanram Harini,
Bhattacharjya Surajit
Publication year - 2008
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21104
Subject(s) - chemistry , cathelicidin , peptide , antimicrobial peptides , nuclear overhauser effect , stereochemistry , circular dichroism , antimicrobial , nuclear magnetic resonance spectroscopy , cyclic peptide , protein secondary structure , protein structure , residue (chemistry) , biochemistry , organic chemistry
Cathelicidins comprise a major family of host‐defense antimicrobial peptides in vertebrates. The C‐terminal part of the cathelicidins is bestowed with antimicrobial and lipopolysaccharide (LPS) neutralizing activities. In this work, we repot high resolution solution structures of two nontoxic active fragments, residues 1–16 or RG16 and residues 8–26 or LK19, of fowlicidin‐1, a cathelicidin family of peptide from chicken, as a complex with LPS using two‐dimensional transferred nuclear Overhauser effect (Tr‐NOE) spectroscopy. Both peptides are highly flexible and do not assume any preferred conformations in their free states. Upon complexation with endotoxin or LPS, peptides undergo structural transitions towards folded conformations. Structure calculations reveal that the LK19 peptide adopts a well defined helical structure with a bend at the middle. By contrast, the first seven amino acids of RG16 are found to be flexible followed by a helical conformation for the residues L8‐A15. In addition, a truncated version of LK19 encompassing residues A15‐K26 or AK12 displays an amphipathic helical structure in LPS. Saturation transfer difference (STD) NMR studies demonstrate that all peptides, RG16, LK19, and AK12, are in close proximity with LPS, whereby the aromatic residues showed the strongest STD effects. Fluorescence studies with fluorescein isothiocyanate (FITC) labeled LPS in the presence of full‐length fowlicidin‐1, LK19, RG16, and AK12 indicated that LPS‐neutralization property of these peptides may result from plausible dissociation of LPS aggregates. The helical structures of peptide fragments derived from fowlicidin‐1 in LPS could be utilized to develop nontoxic antiendotoxic compounds. © 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 9–22, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com