European Biophysics Journal

, Volume 40, Issue 4, pp 529–543 | Cite as

Irregular structure of the HIV fusion peptide in membranes demonstrated by solid-state NMR and MD simulations

  • Dorit Grasnick
  • Ulrich Sternberg
  • Erik Strandberg
  • Parvesh Wadhwani
  • Anne S. UlrichEmail author
Original Paper


To better understand peptide-induced membrane fusion at a molecular level, we set out to determine the structure of the fusogenic peptide FP23 from the HIV-1 protein gp41 when bound to a lipid bilayer. An established solid-state 19F nuclear magnetic resonance (NMR) approach was used to collect local orientational constraints from a series of CF3-phenylglycine-labeled peptide analogues in macroscopically aligned membranes. Fusion assays showed that these 19F-labels did not significantly affect peptide function. The NMR spectra were characteristic of well-behaved samples, without any signs of heterogeneity or peptide aggregation at 1:300 in 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC). We can conclude from these NMR data that FP23 has a well-defined (time-averaged) conformation and undergoes lateral diffusion in the bilayer plane, presumably as a monomer or small oligomer. Attempts to evaluate its conformation in terms of various secondary structures, however, showed that FP23 does not form any type of regular helix or β-strand. Therefore, all-atom molecular dynamics (MD) simulations were carried out using the orientational NMR constraints as pseudo-forces to drive the peptide into a stable alignment and structure. The resulting picture suggests that FP23 can adopt multiple β-turns and insert obliquely into the membrane. Such irregular conformation explains why the structure of the fusion peptide could not be reliably determined by any biophysical method so far.


HIV-1 protein gp41 Membrane fusion Fusogenic peptides Solid-state 19F- and 2H-NMR β-Stranded secondary structure All-atom MD simulations 



We thank Johannes Reichert and Jochen Bürck for their help with the lipid mixing assays, dynamic light scattering measurements, and CD spectroscopy, Sergii Afonin and Olaf Zwernemann for their advice on peptide synthesis and purification, Igor Jakovkin for performing the statistical analysis on the peptide backbone, and Carl Philipp Ulrich for his constructive comments. The project was partially funded by the DFG-Center for Functional Nanostructures (E1.2).

Supplementary material

249_2011_676_MOESM1_ESM.doc (112 kb)
Supplementary material 1 (DOC 113 kb)


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Copyright information

© European Biophysical Societies' Association 2011

Authors and Affiliations

  • Dorit Grasnick
    • 1
  • Ulrich Sternberg
    • 2
  • Erik Strandberg
    • 2
  • Parvesh Wadhwani
    • 2
  • Anne S. Ulrich
    • 1
    • 2
    Email author
  1. 1.Karlsruhe Institute of Technology, Institute of Organic Chemistry and CFNKarlsruheGermany
  2. 2.Karlsruhe Institute of Technology, Institute of Biological Interfaces (IBG-2)KarlsruheGermany

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