Structural and functional analysis of human liver-expressed antimicrobial peptide 2

Henriques, Sonia Troeira, Tan, Chia Chia, Craik, David J. and Clark, Richard J. (2010) Structural and functional analysis of human liver-expressed antimicrobial peptide 2. ChemBioChem, 11 15: 2148-2157. doi:10.1002/cbic.201000400

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Author Henriques, Sonia Troeira
Tan, Chia Chia
Craik, David J.
Clark, Richard J.
Title Structural and functional analysis of human liver-expressed antimicrobial peptide 2
Journal name ChemBioChem   Check publisher's open access policy
ISSN 1439-4227
1439-7633
Publication date 2010-10
Sub-type Article (original research)
DOI 10.1002/cbic.201000400
Volume 11
Issue 15
Start page 2148
End page 2157
Total pages 10
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag GmbH & Co. KGaA
Collection year 2011
Language eng
Abstract Human liver-expressed antimicrobial peptide 2 (LEAP-2) is a cationic antimicrobial peptide (CAMP) believed to have a protective role against bacterial infection. Little is known about the structure-activity relationships of LEAP-2 or its mechanism of action. In this study we describe the structure of LEAP-2, analyze its interaction with model membranes, and relate them to the antimicrobial activity of the peptide. The structure of LEAP-2, determined by NMR spectroscopy, reveals a compact central core with disorder at the N and C termini. The core comprises a β-hairpin and a 310-helix that are braced by disulfide bonds between Cys17-28 and Cys23-33 and further stabilized by a network of hydrogen bonds. Membrane-affinity studies show that LEAP-2 membrane binding is governed by electrostatic attractions, which are sensitive to ionic strength. Truncation studies show that the C-terminal region of LEAP-2 is irrelevant for membrane binding, whereas the N-terminal (hydrophobic domain) and core regions (cationic domain) are essential. Bacterial-growth-inhibition assays reveal that the antimicrobial activity of LEAP-2 correlates with membrane affinity. Interestingly, the native and reduced forms of LEAP-2 have similar membrane affinity and antimicrobial activities; this suggests that disulfide bonds are not essential for the bactericidal activity. This study reveals that LEAP-2 has a novel fold for a CAMP and suggests that although LEAP-2 exhibits antimicrobial activity under low-salt conditions, there is likely to be another physiological role for the peptide. © 2010 Wiley-VCH Verlag GmbH& Co. KGaA, Weinheim.
Keyword Antibiotics
Membranes
NMR spectroscopy
Peptides
Protein structures
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Sun, 05 Dec 2010, 00:15:50 EST