Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37
1998 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 273, no 6, 3718-3724 p.Article in journal (Refereed) Published
The influence of ion composition, pH, and peptide concentration on the conformation and activity of the 37-residue human antibacterial peptide LL-37 has been studied. At micromolar concentration in water, LL-37 exhibits a circular dichroism spectrum consistent with a disordered structure. The addition of 15 mM HCO3-, SO42-, or CF3CO2- causes the peptide to adopt a helical structure, with approximately equal efficiency, while 160 mM Cl- is less efficient, A cooperative transition from disordered to helical structure is observed as the peptide concentration is increased, consistent with formation of an oligomer, The extent of alpha-helicity correlates with the antibacterial activity of LL-37 against both Gram-positive and Gram-negative bacteria. Two homologous peptides, FF-33 and SK-29, containing 4 and 8 residue deletions at the N terminus, respectively, require higher concentrations of anions for helix formation and are less active than LL 37 against Escherichia coli D21. Below pH 5, the helical content of LL-37 gradually decreases, and at pH 2 it is entirely disordered, In contrast, the helical structure is retained at pH over 13. The minimal inhibitory concentration of LL-37 against E. coli is 5 mu M, and at 13-25 mu M the peptide is cytotoxic against several eukaryotic cells, In solutions containing the ion compositions of plasma, intracellular fluid, or interstitial fluid, LL-37 is helical, and hence it could pose a danger to human cells upon release. However, in the presence of human serum, the antibacterial and the cytotoxic activities of LL-37 are inhibited.
Place, publisher, year, edition, pages
1998. Vol. 273, no 6, 3718-3724 p.
antibiotics, bone-marrow, defensins, epithelial-cells, expression, neutrophils, pig intestine, pr-39, protein, secondary structure
IdentifiersURN: urn:nbn:se:sh:diva-29023DOI: 10.1074/jbc.273.6.3718ISI: 000071822300088PubMedID: 9452503ScopusID: 2-s2.0-0032488904OAI: oai:DiVA.org:sh-29023DiVA: diva2:891684
Times Cited: 61 Article English Cited References Count: 37 Yv4272016-01-072016-01-072016-01-11Bibliographically approved