Lipid-specific binding of the calcium-dependent antibiotic daptomycin leads to changes in lipid polymorphism of model membranes

David Jung, Jon Paul Powers, Suzana K. Straus, Robert E.W. Hancock

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)


Daptomycin is a cyclic anionic lipopeptide with an antibiotic activity that is completely dependent on the presence of calcium (as Ca2+). In a previous study [Jung et al., 2004. Chem. Biol. 11, 949-957], it was concluded that daptomycin underwent two Ca2+-dependent structural transitions, whereby the first transition was solely dependent on Ca2+, while the second transition was dependent on both Ca2+ and the presence of negatively charged lipids that allowed daptomycin to insert into and perturb bilayer membranes with acidic character. Differences in the interaction of daptomycin with acidic and neutral membranes were further investigated by spectroscopic means. The lack of quenching of intrinsic fluorescence by the water-soluble quencher, KI, confirmed the insertion of the daptomycin Trp residue into the membrane bilayer, while the kynurenine residue was inaccessible even in an aqueous environment. Differential scanning calorimetry (DSC) indicated that the binding of daptomycin to neutral bilayers occurred through a combination of electrostatic and hydrophobic interactions, while the binding of daptomycin to bilayers containing acidic lipids primarily involved electrostatic interactions. The binding of daptomycin to acidic membranes led to the induction of non-lamellar lipid phases and membrane fusion.

Original languageEnglish
Pages (from-to)120-128
Number of pages9
JournalChemistry and Physics of Lipids
Issue number2
Publication statusPublished or Issued - Aug 2008
Externally publishedYes


  • DSC
  • Daptomycin
  • Fluorescence
  • Lipopeptide
  • Membrane fusion
  • Model membranes
  • P NMR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Cell Biology

Cite this