title: Structure and function of a potent lipopolysaccharide-binding antimicrobial and anti-inflammatory peptide.
abstract: Antimicrobial peptides (AMPs) play pivotal roles in the innate defense of vertebrates. A novel AMP (cathelicidin-PY) has been identified from the skin secretions of the frog Paa yunnanensis . Cathelicidin-PY has an amino acid sequence of RKCNFLCKLKEKLRTVITSHIDKVLRPQG. Nuclear magnetic resonance (NMR) spectroscopy analysis revealed that cathelicidin-PY adopts a tertiary structure with a mostly positively charged surface containing a helix (Thr15-Ser19). It possesses strong antimicrobial activity, low hemolytic activity, low cytotoxicity against RAW 264.7 cells, and strong anti-inflammatory activity. The action of antimicrobial activity of cathelicidin-PY is through the destruction of the cell membrane. Moreover, cathelicidin-PY exerts anti-inflammatory activity by inhibiting the production of nitric oxide (NO) and inflammatory cytokines such as tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Cathelicidin-PY inhibits the activation of Toll-like receptor 4 (TLR4) inflammatory response pathways induced by lipopolysaccharide (LPS). The NMR titration experiments indicated that cathelicidin-PY can bind to LPS. In conclusion, we have identified a novel potent peptide antibiotic with both antimicrobial and anti-inflammatory activities and laid the groundwork for future research and development.
authors.affiliation: Life Sciences College of Nanjing Agricultural University , Nanjing 210095, Jiangsu, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wei
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Yang
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: He
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Mo
authors.forename: Jing
authors.initials: J
authors.lastname: Hong
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Yan
authors.forename: Donghai
authors.initials: D
authors.lastname: Lin
authors.forename: Ren
authors.initials: R
authors.lastname: Lai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001001:Anura; D001419:Bacteria / Q000187:drug effects; D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005658:Fungi / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis; D010802:Phylogeny; D011487:Protein Conformation; D012996:Solutions; D054804:Cathelicidins
chemical_list: D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D008070:Lipopolysaccharides; D012996:Solutions; D009569:Nitric Oxide; D054804:Cathelicidins