Membrane Fusion Intermediates via Directional and Full Assembly of the SNARE Complex

No More Fusion Confusion Biophysical models explain membrane fusion as a sequence of steps—including membrane contact, formation of a fusion stalk (merger of proximal monolayers), development of contact between distal monolayers that may or may not expand (hemifusion), and, finally, rupture of this diaphragm resulting in the opening of a fusion pore. Biological membrane fusion reactions are often driven by so-called SNARE proteins. By using a reconstituted membrane fusion system, Hernandez et al. (p. 1581 , published online 31 May) have now been able to correlate precisely the states of SNARE zippering with intermediate structures along the fusion pathway. The results suggest that a tightly docked state, with a membrane distance so close that no proteins fit in between them, represents a critical fusion intermediate as a consequence of SNARE zippering. This intermediate is incompatible with a SNARE-driven stalk or with a ringlike arrangement of SNAREs depicted in most current models of membrane fusion.