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The effect of fusion inhibitors on the phase behaviour of N-methylated dioleoylphosphatidylethanolamine

Authors
  • Darkes, Malcolm J.M.
  • Harroun, Thad A.
  • Davies, Sarah M.A.
  • Bradshaw, Jeremy P.
Type
Published Article
Journal
Biochimica et Biophysica Acta (BBA) - Biomembranes
Publisher
Elsevier
Publication Date
Jan 01, 2002
Accepted Date
Dec 14, 2001
Volume
1561
Issue
1
Pages
119–128
Identifiers
DOI: 10.1016/S0005-2736(01)00464-3
Source
Elsevier
Keywords
License
Unknown

Abstract

The effects of two fusion inhibitors on the lipid polymorphism of N-methylated dioleoylphosphatidylethanolamine were studied using temperature-resolved, small-angle X-ray diffraction. The inhibitory role of the tri-peptide carbobenzoxy- d-phenylalanine- l-phenylalanine-glycine and the lipid 1-lauroyl-2-hydroxy- sn-glycero-3-phosphocholine in the fusion pathway was studied, using the non-lamellar phase behaviour of the lipid as a model. We used p15EK, the N-terminal region of gp41 from feline leukaemia virus as promoter of membrane fusion, and measured the structural parameters of each observed lipid phase as a function of temperature. The fusion inhibitors were found to impede the expression of negative curvature of lipid monolayers even in the presence of fusion peptide. The results of this study are interpreted in relation to models of the membrane fusion mechanism.

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