A zipper designed to snag

In the current model of vesicle membrane fusion, a helical bundle formed by v- and t-SNARE proteins works like a zipper, drawing closed first at the membrane-distal end, and zipping up toward the membrane-proximal end of the bundle. On page 929, Melia et al. describe the first functional test of this model. Besides confirming that zippering occurs in the membrane-distal to membrane-proximal direction, the results uncover a new regulatory step in vesicle fusion.

The authors examined fusion between liposomes reconstituted with mammalian SNARE proteins and added peptides that bound to either the membrane-proximal COOH terminus or membrane-distal NH₂ terminus of the t-SNARE. As predicted by the model, the NH₂- directed peptides block initial contact between v- and t-SNARES and inhibit fusion, but, once zippering has started, fusion is resistant to these NH₂-directed peptides....