Changes in Lipid Bilayer Dynamics caused by the HIV-1 Fusion Peptide

HIV-1 fusion with a cell membrane involves the interaction between a sequence from the gp41 capsid protein, termed the fusion peptide (FP), and the membrane. To better understand how this transition drives fusion, the interaction between a variant of the HIV-1 gp41 FP with vesicles was studied using neutron spin echo spectroscopy, small-angle neutron scattering and circular dichroism spectroscopy. In the model membrane studied here, the FP associates with membranes as an alpha-helix at the relatively low peptide-to-lipid ratio of 1/200, but was observed to possess a beta-sheet structure at a peptide-to-lipid ratio of 1/50. The concentration-dependent helix-to-sheet transition correlates with slower vesicle dynamics that are consistent with a more rigid vesicle structure. The results provide new insight into how the FP conformational transition drives vesicle fusion.

Neutron beam time for this research has been allocated by the Jülich Center for Neutron Science, JCNS1, Jülich Forschungszentrum GmbH, Germany, outstation to the Spallation Neutron Source (SNS), Oak Ridge, TN. This research used resources at the Spallation Neutron Source, A DOE Office of Science User Facility operated by the Oak Ridge National Laboratory.