Membrane thinning effect of the β-sheet antimicrobial protegrin

William T. Heller, Alan J. Waring, Robert I. Lehrer, Thad A. Harroun, Thomas M. Weiss, Lin Yang, Huey W. Huang

Research output: Contribution to journalArticlepeer-review

183 Scopus citations

Abstract

Lipid bilayers containing the antimicrobial peptide protegrin-1 (PG-1) were studied by lamellar X-ray diffraction. Previously, we have shown that the peptide exists in two distinct states when associated with lipid bilayers depending on the peptide concentration [Heller, W. T., Waring, A. J., Lehrer, R. I., and Huang, H. W. (1998) Biochemistry 37, 17331-17338]. For concentrations below a lipid-dependent threshold, PG-1 exhibits a unique oriented circular dichroism spectrum called the S state. X-ray experiments show that in this state PG-1 decreases the thickness of the lipid bilayer in proportion to the peptide concentration, similar to alamethicin's membrane thinning effect. This indicates that the S state is adsorbed in the headgroup region of the lipid bilayer, where the peptide is in an inactive state. For PG-1 above the threshold concentration, X-ray diffraction shows that the interaction between the peptide and the bilayer changes significantly. These results suggest that PG-1 has the same concentration-gated mechanism of action as alamethicin.

Original languageEnglish
Pages (from-to)139-145
Number of pages7
JournalBiochemistry
Volume39
Issue number1
DOIs
StatePublished - Jan 11 2000
Externally publishedYes

Funding

FundersFunder number
National Institute of General Medical SciencesR01GM055203, T32GM008280
National Institute of Allergy and Infectious DiseasesP01AI037945

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