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Insight into the antimicrobial activities of coprisin isolated from the dung beetle, Copris tripartitus, revealed by structure–activity relationships
- Source :
- Biochimica et Biophysica Acta (BBA) - Biomembranes. 1828:271-283
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- The novel 43-residue, insect defensin-like peptide coprisin, isolated from the dung beetle, Copris tripartitus, is a potent antibiotic with bacterial cell selectivity, exhibiting antimicrobial activities against Gram-positive and Gram-negative bacteria without exerting hemolytic activity against human erythrocytes. Tests against Staphylococcus aureus using fluorescent dye leakage and depolarization measurements showed that coprisin targets the bacterial cell membrane. To understand structure-activity relationships, we determined the three-dimensional structure of coprisin in aqueous solution by nuclear magnetic resonance spectroscopy, which showed that coprisin has an amphipathic α-helical structure from Ala(19) to Arg(28), and β-sheets from Gly(31) to Gln(35) and Val(38) to Arg(42). Coprisin has electropositive regions formed by Arg(28), Lys(29), Lys(30), and Arg(42) and ITC results proved that coprisin and LPS have electrostatically driven interactions. Using measurements of nitric oxide release and inflammatory cytokine production, we provide the first verification of the anti-inflammatory activity and associated mechanism of an insect defensin, demonstrating that the anti-inflammatory actions of the defensin-like peptide, coprisin, are initiated by suppressing the binding of LPS to toll-like receptor 4, and subsequently inhibiting the phosphorylation of p38 mitogen-activated protein kinase and nuclear translocation of NF-kB. In conclusion, we have demonstrated that an amphipathic helix and an electropositive surface in coprisin may play important roles in its effective interaction with bacterial cell membranes and, ultimately, in its high antibacterial activity and potent anti-inflammatory activity. In addition to elucidating the antimicrobial action of coprisin, this work may provide insight into the mechanism of action of insect defense systems.
- Subjects :
- Keratinocytes
Lipopolysaccharides
Staphylococcus aureus
Magnetic Resonance Spectroscopy
Protein Conformation
Molecular Sequence Data
Biophysics
Peptide
Biology
Nitric Oxide
p38 Mitogen-Activated Protein Kinases
Biochemistry
Protein Structure, Secondary
Bacterial cell structure
Cell Line
Microbiology
Mice
Structure-Activity Relationship
Anti-inflammatory activity
Protein structure
Anti-Infective Agents
medicine
Animals
Humans
Structure–activity relationship
Amino Acid Sequence
Protein kinase A
Defensin
Inflammation
chemistry.chemical_classification
Sequence Homology, Amino Acid
Macrophages
NF-kappa B
Structure
Cell Biology
NMR
Coleoptera
Toll-Like Receptor 4
chemistry
Mechanism of action
Cytokines
Insect Proteins
Insect defensin
medicine.symptom
Peptides
Antimicrobial peptide
Antibacterial activity
Subjects
Details
- ISSN :
- 00052736
- Volume :
- 1828
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Biomembranes
- Accession number :
- edsair.doi.dedup.....11b68ff97a28e758abf03c53952208ea