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Cover       It has been known for some time that SNAREs are central players in membrane traffic. Most SNAREs are C-terminally anchored integral membrane proteins capable of entering into coiled-coil interactions with other SNAREs. Distinct SNARE family members are arrayed on particular membranes around the cell, and studies suggest that they act late in vesicular traffic, close to the point of membrane fusion. One way to classify SNAREs is to divide them into those that travel between donor and acceptor compartments on vesicles, the v-SNAREs, and those that reside predominantly on the target membrane, the t-SNAREs. Complexes of v- and t-SNAREs have been found in cells and were originally interpreted as intermediates on the way to membrane fusion. In an effort to understand SNARE complex structure, P. Hanson, R. Roth, H. Morisaki, R. Jahn, and J. Heuser ([1997] Structure and conformational changes in NSF and its membrane receptor complexes visualized by quick-freeze/deep-etch electron microscopy. Cell 90, 523-535) undertook quick-freeze/deep-etch electron microscopy of neuronal SNARE complexes containing syntaxin, SNAP-25 and synaptobrevin. Hanson et al. assembled SNARE complexes that contained an "EM-tag" (the readily-visualized globular maltose binding protein) on either the N- or C-terminus of syntaxin (a t-SNARE) and added IgG that recognized the N- or C-terminus of synaptobrevin (a v-SNARE). The upper panel shows two SNARE complexes, held together with an antibody that binds the C-terminus of synaptobrevin (antibody forms the apex, pink); the ball-like maltose binding protein-tags can be seen at the N-terminus of syntaxin (yellow). This and other images indicated that v- and t-SNAREs interact in parallel; that is, all the SNARE transmembrane domains are at one end. The parallel arrangement was confirmed at atomic resolution with the solution of the X-ray structure of the coiled-coil region of the neuronal SNARE complex (lower panel; R. Sutton, D. Fasshauer, R. Jahn, A. Brnger [1998]. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution. Nature 395, 347-353. The structure shows that the SNARE complex is a parallel four-alpha-helix bundle (Sx, the syntaxin alpha-helix; Sb, the synaptobrevin alpha-helix; Sn1 & Sn2, the SNAP-25 alpha-helices). These studies have been very influential because they provide a plausible mechanism for SNARE-mediated membrane fusion. One hypothesis is that assembly of parallel SNARE complexes between the vesicle and target membranes would result in close approach of the membranes and might provide the force required for membrane fusion.Gerry Waters