Our primary focus is to understand the molecular mechanism of synaptic neurotransmission, and how this process is controlled and regulated by a set of dynamically interacting proteins. Vesicle fusion occurs in several stages: tethering, docking, priming, and calcium-dependent fusion. We are investigating the proteins involved at each of these stages by X-ray crystallography, nuclear magnetic resonance, and other spectroscopic methods. We have recently determined the crystal structure of a core of the synaptic fusion complex of syntaxin, synaptobrevin, and SNAP-25 (Sutton, et al. Nature 395, 347-353, 1998). The SNARE proteins are the target of the protease domains of the botulinum and tetanus clostridial neurotoxins. The SNARE complex plays an essential role in the fusion of synaptic vesicles with the pre-synaptic membrane. The assembly of the synaptic fusion complex is associated with a dramatic increase in stability. The free energy released by the assembly could lead to membrane fusion. These proteins and their accessory proteins will be the subject of the seminar.