LEAP2 binds bacteria

Stable Identifier
Reaction [binding]
Homo sapiens
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Liver-expressed antimicrobial peptide 2 (LEAP2) is a cationic peptide, which is believed to have a protective function against bacterial infection (Krause A et al. 2003; Henriques ST et al. 2010; Hocquellet A et al. 2010). LEAP2, originally isolated from human blood, is expressed predominantly in the liver but is also produced by a wide range of other tissues and organs, including the kidney and the intestinal tract (Krause A et al. 2003; Howard A et al. 2010).

Structural analysis of LEAP2 revealed a compact central core stabilized by two disulfide bonds between Cys17-28 and Cys23-33 and a network of hydrogen bonds (Henriques ST et al. 2010; Hocquellet A et al. 2010). The central core of LEAP2 contains the majority of the arginine and lysine residues, which are clustered to form an extended, positively-charged patch on the surface of the molecule (Henriques ST et al. 2010). The terminal segments of LEAP2 are relatively unstructured and contain the majority of the hydrophobic residues (Henriques ST et al. 2010). Membrane-affinity studies show that LEAP2 membrane binding is governed by electrostatic attractions, which are sensitive to ionic strength. Truncation studies found that the C-terminal region of LEAP2 is irrelevant for both membrane binding and antimicrobial activity, whereas the N-terminal (hydrophobic domain) and core regions (cationic domain) are essential (Henriques ST et al. 2010).

LEAP2 showed antimicrobial activity against Bacillus subtilis at low ionic strength (Henriques ST et al. 2010). The inability of LEAP2 to inhibit B. subtilis growth at physiologically relevant salt concentration is consistent with a proposed electrostatic contribution to membrane binding (Henriques ST et al. 2010). Other bacteria such as Gram-positive Bacillus megaterium, Staphylococcus carnosus, Micrococcus luteus and Gram-negative Neisseria cinerea are also sensitive to treatment with LEAP2 (Krause A et al. 2003). Furthermore, the native and reduced forms of LEAP2 show similar membrane affinity and antimicrobial activities; this suggests that disulfide bonds are not essential for bactericidal activity (Henriques ST et al. 2010; Hocquellet A et al. 2010). LEAP2 did not affect the growth of Escherichia coli and S. aureus at physiological or low ionic strength (Henriques ST et al. 2010). LEAP2 was found to be inactive against Pseudomonas fluorescens (Krause A et al. 2003). The antimicrobial potential of LEAP2 against E. coli, B. subtilis, B. megaterium, and M. luteus was significantly lower than that of cathelicidin LL37 (Hocquellet A et al. 2010). Further study is needed to clarify the antimicrobial activity of LEAP2.

LEAP2 is highly conserved throughout vertebrates, particularly in mammals suggesting that LEAP2 has additional physiological functions that remain to be elucidated (Krause A et al. 2003; Zhang YA et al. 2004; Townes CL et al. 2009; Henriques ST et al. 2010).

Literature References
PubMed ID Title Journal Year
12493837 Isolation and biochemical characterization of LEAP-2, a novel blood peptide expressed in the liver

Sillard, R, Adermann, K, Kleemeier, B, Wattler, F, Conejo-García, JR, Forssmann, WG, Klüver, E, Maronde, E, Krause, A, Wattler, S, Schulz-Knappe, P, Nehls, MC

Protein Sci. 2003
20845358 Structural and functional analysis of human liver-expressed antimicrobial peptide 2

Clark, RJ, Tan, CC, Henriques, ST, Craik, DJ

Chembiochem 2010
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