Molecular View of the Role of Fusion Peptides in Promoting Positive Membrane Curvature

Marc Fuhrmans, Siewert J. Marrink*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

68 Citations (Scopus)
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Abstract

Fusion peptides are moderately hydrophobic segments of viral and nonviral membrane fusion proteins that enable these proteins to fuse two closely apposed biological membranes. In vitro assays furthermore show that even isolated fusion peptides alone can support membrane fusion in model systems. In addition, the fusion peptides have a distinct effect on the phase diagram of lipid mixtures. Here, we present molecular dynamics simulations investigating the effect of a particular fusion peptide, the influenza hemagglutinin fusion peptide and some of its mutants, on the lipid phase diagram. We detect a systematic shift toward phases with more positive mean curvature in the presence of the peptides, as well as an occurrence of bicontinuous cubic phases, which indicates a stabilization of Gaussian curvature. The wild-type fusion peptide has a stronger effect on the phase behavior as compared to the mutants, which we relate to its boomerang shape. Our results point to a different role of fusion peptides than hitherto assumed, the stabilization of pores rather than stalks along the fusion pathway.

Original languageEnglish
Pages (from-to)1543-1552
Number of pages10
JournalJournal of the American Chemical Society
Volume134
Issue number3
DOIs
Publication statusPublished - 25-Jan-2012

Keywords

  • INFLUENZA-VIRUS HEMAGGLUTININ
  • MODEL MEMBRANES
  • ANTIMICROBIAL PEPTIDES
  • DYNAMICS SIMULATION
  • MEDIATED FUSION
  • CONFORMATIONAL-CHANGE
  • MECHANISM
  • HEMIFUSION
  • BILAYERS
  • DOMAIN

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