2LN4

Insight into the antimicrobial activities based on the Structure-activity relationships of coprisin isolated from the Dung Beetle, Copris tripartitus

Summary for 2LN4

• Entry DOI: 10.2210/pdb2ln4/pdb
• NMR Information: BMRB: 18146
• Descriptor: Coprisin (1 entity in total)
• Functional Keywords: antimicrobial protein, coprisin, defensin-like peptide
• Biological source: Copris tripartitus
• Total number of polymer chains: 1
• Total formula weight: 4482.29

Authors

Kim, Y.,Kim, J.K.,Lee, E. (deposition date: 2011-12-16, release date: 2012-11-28, Last modification date: 2024-11-20)

Primary citation

Lee, E.,Kim, J.K.,Shin, S.,Jeong, K.W.,Shin, A.,Lee, J.,Lee, D.G.,Hwang, J.S.,Kim, Y.
Insight into the antimicrobial activities of coprisin isolated from the dung beetle, Copris tripartitus, revealed by structure-activity relationships
Biochim.Biophys.Acta, 2012

PubMed 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.

PubMed: 23137439
DOI: 10.1016/j.bbamem.2012.10.028

Experimental method

SOLUTION NMR