The SNARE complex is critical for vesicle fusion, notably during release of neurotransmitters at synapses. Understanding the biophysics of SNARE assembly has been the object of several structural studies, and yet much remains to be understood about the mechanisms. Now, Gao et al. (see the Perspective by Rizo) describe the results of cell-free experiments using optical tweezers to elucidate assembly and disassembly of the SNARE complex. Direct observations of SNARE intermediates revealed multiple steps of the assembly process, along with the associated energetics and kinetics. Applying forces similar to those occurring during fusion, an intermediate was stabilized, and the derived mechanism indicates how neurotransmitter release may be regulated.
Y. Gao, S. Zorman, G. Gundersen, Z. Xi, L. Ma, G. Sirinakis, J. E. Rothman, Y. Zhang, Single reconstituted neuronal SNARE complexes zipper in three distinct stages. Science 337, 1340–1343 (2012). [Abstract] [Full Text]