Biophysical Studies Reveal Key Interactions between Papiliocin-Derived PapN and Lipopolysaccharide in Gram-Negative Bacteria
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Papiliocin, isolated from the swallowtail butterfly (Papilio xuthus), is an antimicrobial peptide with high selectivity against gram-negative bacteria. We previously showed that the Nterminal helix of papiliocin (PapN) plays a key role in the antibacterial and anti-inflammatory activity of papiliocin. In this study, we measured the selectivity of PapN against multidrugresistant gram-negative bacteria, as well as its anti-inflammatory activity. Interactions between Trp2 of PapN and lipopolysaccharide (LPS), which is a major component of the outer membrane of gram-negative bacteria, were studied using the Trp fluorescence blue shift and quenching in LPS micelles. Furthermore, using circular dichroism, we investigated the interactions between PapN and LPS, showing that LPS plays critical roles in peptide folding. Our results demonstrated that Trp2 in PapN was buried deep in the negatively charged LPS, and Trp2 induced the α-helical structure of PapN. Importantly, docking studies determined that predominant electrostatic interactions of positively charged arginine residues in PapN with phosphate head groups of LPS were key factors for binding. Similarly, hydrophobic interactions by aromatic residues of PapN with fatty acid chains in LPS were also significant for binding. These results may facilitate the development of peptide antibiotics with antiinflammatory activity.
Abstract
Papiliocin, isolated from the swallowtail butterfly (Papilio xuthus), is an antimicrobial peptide with high selectivity against gram-negative bacteria. We previously showed that the Nterminal helix of papiliocin (PapN) plays a key role in the antibacterial and anti-inflammatory activity of papiliocin. In this study, we measured the selectivity of PapN against multidrugresistant gram-negative bacteria, as well as its anti-inflammatory activity. Interactions between Trp2 of PapN and lipopolysaccharide (LPS), which is a major component of the outer membrane of gram-negative bacteria, were studied using the Trp fluorescence blue shift and quenching in LPS micelles. Furthermore, using circular dichroism, we investigated the interactions between PapN and LPS, showing that LPS plays critical roles in peptide folding. Our results demonstrated that Trp2 in PapN was buried deep in the negatively charged LPS, and Trp2 induced the α-helical structure of PapN. Importantly, docking studies determined that predominant electrostatic interactions of positively charged arginine residues in PapN with phosphate head groups of LPS were key factors for binding. Similarly, hydrophobic interactions by aromatic residues of PapN with fatty acid chains in LPS were also significant for binding. These results may facilitate the development of peptide antibiotics with antiinflammatory activity.
참고문헌 (30)
- Hancock REW, "Modulating immunity as a therapy for bacterial infections", Nat. Rev. Microbiol., 10, pp.243~254 (2012)[DOI]
- Haney EF, "Antimicrobial peptides: an introduction;Antimicrobial Peptides. Methods in Molecular Biology, Vol. 1548", pp.3~22 (2017), Humana Press
- Koehbach J, "Structure-activity relationships of insect defensins", Front. Chem., 5, pp.45~ (2017)[DOI]
- Yi HY, "Insect antimicrobial peptides and their applications", Appl. Microbiol. Biotechnol., 98, pp.5807~5822 (2014)[DOI]
- Seong Ryul Kim, "Characterization and cDNA Cloning of a Cecropin-Like Antimicrobial Peptide, Papiliocin, from the Swallowtail Butterfly, Papilio xuthus", Molecules and Cells, 29(4), pp.419~423 (2010), 한국분자세포생물학회
- Kim JK, "Structure and function of papiliocin with antimicrobial and anti-inflammatory activities isolated from the swallowtail butterfly, Papilio xuthus", J. Biol. Chem., 286, pp.41296~41311 (2011)[DOI]
- Lee J, "Influence of the papiliocin peptide derived from Papilio xuthus on the perturbation of fungal cell membranes", FEMS Microbiol Lett., 311, pp.70~75 (2010)[DOI]
- Lee E, "Functional roles of aromatic residues and helices of papiliocin in its antimicrobial and anti-inflammatory activities", Sci. Rep., 5, pp.12048~ (2015)[DOI]
- 전다솜, "Short Antimicrobial Peptides Exhibiting Antibacterial and Anti-Inflammatory Activities Derived from the N-Terminal Helix of Papiliocin", Bulletin of the Korean Chemical Society, 38(11), pp.1260~1268 (2017), 대한화학회[DOI]
- Bowdish DM, "Immunomodulatory activities of small host defense peptides", Antimicrob. Agents Chemother., 49, pp.1727~1732 (2005)[DOI]
- Rosenfeld Y, "Endotoxin (lipopoly- saccharide) neutralization by innate immunity host-defense peptides. Peptide properties and plausible modes of action", J. Biol. Chem., 281, pp.1636~1643 (2006)[DOI]
- Nell MJ, "Development of novel LL-37 derived antimicrobial peptides with LPS and LTA neutralizing and antimicrobial activities for therapeutic application", Peptides, 27, pp.649~660 (2006)[DOI]
- Frohm M, "The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders", J. Biol. Chem., 272, pp.15258~15263 (1997)[DOI]
- Lee PH, "Expression of an additional cathelicidin antimicrobial peptide protects against bacterial skin infection", Proc. Natl. Acad. Sci. USA, 102, pp.3750~3755 (2005)[DOI]
- Brandenburg K, "Peptides with dual mode of action: killing bacteria and preventing endotoxin-induced sepsis", Biochim. Biophys. Acta, 1858, pp.971~979 (2016)[DOI]
- Terayama T, "Polymyxin B hemoperfusion for sepsis and septic shock: a systematic review and meta-analysis", Surg. Infect., 18, pp.225~233 (2017)[DOI]
- Lee E, "Insight into the antimicrobial activities of coprisin isolated from the dung beetle, Copris tripartitus, revealed by structure-activity relationships", Biochim. Biophys. Acta, 1828, pp.271~283 (2013)[DOI]
- Jeon D, "Investigation of cationicity and structure of pseudin-2 analogues for enhanced bacterial selectivity and anti-inflammatory activity", Sci. Rep., 7, pp.1455~ (2017)[DOI]
- nitrate in biological fluids, "Anal. Biochem.", 1982, 131~138, 10.1016[DOI]
- Jnawali HN, "Anti-inflammatory activity of rhamnetin and a model of its binding to c-Jun NH2-terminal kinase 1 and p38 MAPK", J. Nat. Prod., 77, pp.258~263 (2014)[DOI]
- Trott O, "AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading", J. Comput. Chem., 31, pp.455~461 (2010)
- Dassault Systemes BIOVIA, "Discovery Studio, 4.1" (2015), Dassault Systemes
- Lee CC, "Accessory molecules for Toll-like receptors and their function", Nat. Rev. Immunol., 12, pp.168~179 (2012)[DOI]
- Kondo T, "Dissecting negative regulation of Toll-like receptor signaling", Trends Immunol., 33(9), pp.449~458 (2012)[DOI]
- O’Neill LA, "Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer", Pharmacol. Rev., 61, pp.177~197 (2009)[DOI]
- Bhunia A, "NMR structure of pardaxin, a pore- forming antimicrobial peptide, in lipopolysaccharide micelles: mechanism of outer membrane permeabilization", J. Biol. Chem., 285, pp.3883~3895 (2010)[DOI]
- Sudheendra US, "Membrane disruptive antimicrobial activities of human <TEX>${\beta}$<", TEX>-defensin-3 analogs, 2014, pp.91, 91~99
- Baek MH, "Lipopolysaccharide-bound structure of the antimicrobial peptide cecropin P1 determined by nuclear magnetic resonance spectroscopy", J. Pept. Sci., 22, pp.214~221 (2016)[DOI]
- Ghosh A, "NMR structure and binding of esculentin-1a(1-21)<TEX>$NH_2$<", TEX> and its diastereomer to lipopolysaccharide: correlation with biological functions, 2016, pp.1858, 800~812
- Kushibiki T, "Interaction between tachyplesin I, an antimicrobial peptide derived from horseshoe crab, and lipopolysaccharide", Biochim. Biophys. Acta, 1844, pp.527~534 (2014)[DOI]