The SNARE Motif of Synaptobrevin Exhibits an Aqueous–Interfacial Partitioning That Is Modulated by Membrane Curvature

[Image: see text] The structure and interfacial association of the full-length vesicle SNARE, synaptobrevin, were compared in four different lipid environments using nuclear magnetic resonance and electron paramagnetic resonance spectroscopy. In micelles, segments of the SNARE motif are helical and associated with the interface. However, the fraction of helix and interfacial association decreases as synaptobrevin is moved from micelle to bicelle to bilayer environments, indicating that the tendency toward interfacial association is sensitive to membrane curvature. In bilayers, the SNARE motif of synaptobrevin transiently associates with the lipid interface, and regions that are helical in micelles are in conformational and environmental exchange in bicelles and bilayers. This work demonstrates that the SNARE motif of synaptobrevin has a significant propensity to form a helix and exchange with the membrane interface prior to SNARE assembly. This transient interfacial association and its sensitivity to membrane curvature are likely to play a role in SNARE recognition events that regulate membrane fusion.