Published online 20 July 2005
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Structural and DNA-binding studies on the bovine antimicrobial peptide, indolicidin: evidence for multiple conformations involved in binding to membranes and DNA
1Institute of Biological Chemistry, Academia Sinica Taipei, Taiwan 2Institute of Biomedical Sciences, Academia Sinica Taipei, Taiwan 3Institute of Biochemical Sciences, National Taiwan University Taipei, Taiwan
*To whom correspondence should be addressed. Tel: +886 2 2785 5696, ext. 7101; Fax: +886 2 2653 9142; Email: shwu{at}gate.sinica.edu.tw
Received April 1, 2005. Revised June 24, 2005. Accepted July 5, 2005.
Indolicidin, a l3-residue antimicrobial peptide-amide, which is unusually rich in tryptophan and proline, is isolated from the cytoplasmic granules of bovine neutrophils. In this study, the structures of indolicidin in 50% D3-trifluoroethanol and in the absence and presence of SDS and D38-dodecylphosphocholine were determined using NMR spectroscopy. Multiple conformations were found and were shown to be due to different combinations of contact between the two WPW motifs. Although indolicidin is bactericidal and able to permeabilize bacterial membranes, it does not lead to cell wall lysis, showing that there is more than one mechanism of antimicrobial action. The structure of indolicidin in aqueous solution was a globular and amphipathic conformation, differing from the wedge shape adopted in lipid micelles, and these two structures were predicted to have different functions. Indolicidin, which is known to inhibit DNA synthesis and induce filamentation of bacteria, was shown to bind DNA in gel retardation and fluorescence quenching experiments. Further investigations using surface plasmon resonance confirmed the DNA-binding ability and showed the sequence preference of indolicidin. Based on our biophysical studies and previous results, we present a diagram illustrating the DNA-binding mechanism of the antimicrobial action of indolicidin and explaining the roles of the peptide when interacting with lipid bilayers at different concentrations.
Correspondence may also be addressed to Chinpan Chen. Tel: +886 2 2652 3035; Fax: +886 2 2788 7641; Email: bmchinp{at}ibms.sinica.edu.tw
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