Structure, location, and lipid perturbations of melittin at the membrane interface

Kalina A Hristova, Christopher E. Dempsey, Stephen H. White

Research output: Contribution to journalArticle

Abstract

Melittin is arguably the most widely studied amphipathic, membrane-lytic α-helical peptide. Although several lines of evidence suggest an interfacial membrane location at low concentrations, melittin's exact position and depth of penetration into the hydrocarbon core are unknown. Furthermore, the structural basis for its lytic action remains largely a matter of conjecture. Using a novel x-ray absolute-scale refinement method, we have now determined the location, orientation, and likely conformation of monomeric melittin in oriented phosphocholine lipid multilayers. Its helical axis is aligned parallel to the bilayer plane at the depth of the glycerol groups, but its average conformation differs from the crystallographic structure. As observed earlier for another amphipathic α-helical peptide, the lipid perturbations induced by melittin are remarkably modest. Small bilayer perturbations thus appear to be a general feature of amphipathic helices at low concentrations. In contrast, a dimeric form of melittin causes larger structural perturbations under otherwise identical conditions. These results provide direct structural evidence that self-association of amphipathic helices may be the crucial initial step toward membrane lysis.

Original languageEnglish (US)
Pages (from-to)801-811
Number of pages11
JournalBiophysical Journal
Volume80
Issue number2
StatePublished - 2001
Externally publishedYes

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Melitten
Lipids
Membranes
Peptides
Phosphorylcholine
Hydrocarbons
Glycerol
X-Rays

ASJC Scopus subject areas

  • Biophysics

Cite this

Structure, location, and lipid perturbations of melittin at the membrane interface. / Hristova, Kalina A; Dempsey, Christopher E.; White, Stephen H.

In: Biophysical Journal, Vol. 80, No. 2, 2001, p. 801-811.

Research output: Contribution to journalArticle

Hristova, Kalina A ; Dempsey, Christopher E. ; White, Stephen H. / Structure, location, and lipid perturbations of melittin at the membrane interface. In: Biophysical Journal. 2001 ; Vol. 80, No. 2. pp. 801-811.
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