Atomic-Resolution Simulations Yield New Insight into Vesicle Fusion and Fusion Protein Mechanisms

Abstract

Membrane fusion is critical to both cellular vesicle trafficking and infection by enveloped viruses. While the fusion protein assemblies that catalyze fusion are readily identifiable, the specific activities of the different proteins involved and nature of the membrane changes they induce remains unknown. Here, we report many atomic-resolution molecular dynamics simulations of both fusion by a pair of vesicles and assemblies of influenza fusion peptides in planar bilayers. The mechanism of fusion in our simulations is roughly consistent with the stalk hypothesis for fusion, but we observe several new features that help explain the mechanism of fusion proteins. Our high-resolution simulations yield new structural intermediates that differ substantially from continuum models of fusion and give specific structural details for the membrane-altering effects of fusion proteins. These results may yield a common mechanistic pathway for structurally diverse classes of fusion proteins.