Rapid and efficient fusion of phospholipid vesicles by the alpha-helical core of a SNARE complex in the absence of an N-terminal regulatory domain

A protease-resistant core domain of the neuronal SNARE complex consists of an alpha-helical bundle similar to the proposed fusogenic core of viral fus ion proteins [Skehel, J. J. & Wiley, D. C. (1998) Cell 95, 871-874]. We fin d that the isolated core of a SNARE complex efficiently fuses artificial bi layers and does so faster than full length SNAREs. Unexpectedly, a dramatic increase in speed results from removal of the N-terminal domain of the t-S NARE syntaxin, which does not affect the rate of assembly of v-t SNARES. In the absence of this negative regulatory domain, the half-time for fusion o f an entire population of lipid vesicles by isolated SNARE cores (approxima te to 10 min) is compatible with the kinetics of fusion in many cell types.